Abstract
Radiation inactivation of enveloped viruses occurs as the result of damages at the molecular level of their genome. The rapidly emerging and ongoing coronavirus disease 2019 (COVID-19) pneumonia pandemic prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global health crisis and an economic devastation. The readiness of an active and safe vaccine against the COVID-19 has become a race against time in this unqualified global panic caused by this pandemic. In this review, which we hope will be helpful in the current situation of COVID-19, we analyze the potential use of γ-irradiation to inactivate this virus by damaging at the molecular level its genetic material. This inactivation is a vital step towards the design and development of an urgently needed, effective vaccine against this disease.
Keywords: SARS-CoV-2 virus, virus genome, virus infectivity, gamma irradiation, virus inactivation, vaccine development
1. Introduction
Viruses (or virions) are subcellular particles, commonly spherical or rod-shaped, which composed of a protein capsid that contains their genetic material made of RNA or DNA. Sometimes the viral genome is protected by an additional outer envelope made of a lipid bilayer with spikes of glycoproteins inserted inside the viral envelope [1]. Viruses are classified based on their size, shape, envelope, and structure of their genome. Unlike bacteria, viruses lack cell organelles and thus have no metabolic activities on their own. To transcript and replicate, they entirely depend on the host biochemical machinery of eukaryotic or prokaryotic host cells [2]. Once inside the host cell, viruses can mutate through genome deletion, insertion, and/or substitution to novel strains of different virulence [3,4]. This viral mutation is the major obstacle for the development of new vaccines [5,6].
1.1. Key features of human coronavirus
Six human coronaviruses (HCoVs) were known before the COVID-19 outbreak: 229E and NL63 (alpha coronavirus), OC43, HKU1, SARS-CoV, and MERS-CoV (beta coronavirus) [7]. Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) first emerged in South China in 2002–2003 to cause a large-scale epidemic with over 8,000 infections and more than 800 deaths [8]. The Middle East Respiratory Syndrome CoV (MERS-CoV) has caused a persistent epidemic in the Arabian Peninsula, especially in Saudi Arabia in 2012 [9]. SARS-CoV and MERS-CoV are enveloped positive-sense RNA viruses (size ranging from 70 to 90 nm) belonging to the Coronaviridae family. It was shown that rodents, avians, and mainly bats are reservoir host of these family viruses that can be potentially transmitted from animals to humans [10,11] due to the growing consumption of animal proteins including those from exotic wild mammals in China.
A novel strain of coronavirus, labeled as SARS-CoV-2 by the International Committee on Taxonomy of Viruses-Coronavirus Study Group [12], belonging to the beta-coronavirus lineage, shares around 80% identity to SARS-CoV [13,14]. This strain, believed to have started from a seafood market in the city of Wuhan, China, in December 2019, is now spreading and creating a chaos across the entire world [15,16]. Human-to-human transmission of this virus was officially confirmed on January 20th 2020 [10]. World Health Organization (WHO) declared this disease as a global pandemic on March 11, 2020 [17]. As of 29 January 2021, 27,901,760 cases are still active, 72,337,017 recovered, and 2,210,259 died in 235 countries or territories worldwide [18].
Similar to previous coronaviruses symptoms, SARS-CoV-2 is mainly affecting the lower respiratory track, ranging from mild respiratory disease to SARS and septic shock in advanced stages. Damages to the cardiovascular system, gut, kidneys, and brain have also been reported [13,19] along with vital organ failures in comorbid patients [20,21].
The genetic material of SARS-CoV-2 consists of single-stranded RNA backbone made of alternating 5-carbon sugar (ribose) and phosphate groups. Attached to this backbone are 29,891 to 29,903 adenine, uracil, cytosine, and guanine bases [22,23] encoding for 9,860 amino acids [10]. One third of the SARS-CoV-2 genome make up the four major structural proteins: spike glycoprotein (S), membrane protein (M), envelope protein (E), and nucleocapsid protein (N) accountable for some important functions in virus replication [24,25]. The remaining two‐thirds of its viral genome encode for 16 nonstructural proteins (nsp-1 to 16). Each of these nsps has a specific role in the life cycle of the virus and its pathogenicity [26,27]. For instance, nsp-1 is used by the virus to elude the host innate immune system [28], nsp-2 is indispensable for its replication, and nsp-9, in complex with nsp-8, is involved in RNA replication and virulence [29].
There is a 76.5% similarity in the amino acid sequences of the spike glycoprotein in SARS-CoV and SARS-CoV-2 [30]. SARS-CoV-2 seems to have greater binding affinity to the angiotensin converting enzyme 2 (ACE2) cell membrane receptor than the other SARS-CoV virus strains, suggesting a greater capacity of SARS-CoV-2 for human to human transmission [31,32]. There are speculations that cellular overexpression of human ACE2 (associated with the usage of medications such as ACE2 inhibitors, angiotensin II receptor blockers) could enhance the COVID-19 severity [21,33,34,35,36]. Among the four structural proteins of the SARS-CoV family, the spike glycoprotein S plays a key role in viral docking and cellular internalization [37]. It binds via the receptor-binding domain (RBD) in the S1 subunit to the ACE2 receptors [38,39], expressed especially on the plasma membrane of human respiratory epithelial host cells, and virtually in all other organs. The virus penetrates the host cell via endocytosis through its S2 subunit [40,41] and infects it by hijacking its molecular machinery to encode for RNA polymerase enzyme necessary for the replication of its own RNA genome [42,43]. Viral entry in cells is a critical phase in the course of the COVID-19 disease. Thus, inhibition of the viral binding and internalization in a host cell constitute a strategy for potential therapeutics against COVID-19 pandemic.
1.2. SARS-CoV-2 infectivity
Aerial transmission by expelled respiratory droplets is considered as the main direct transmission vector of the SARS-CoV-2 when in close contact with an infected person coughing, sneezing, or even talking [10,44,45,46]. Some findings have indicated that the virus may as well be airborne [31,47,48]. Indirect transmission may also occur via fomites when respiratory droplets from infected people land on object surfaces which can be touched by a receptive host [49,50].
The WHO recommends that SARS CoV-2 sample handling should be conducted in no less than a Biosafety Level 3 (BSL-3) laboratory using BSL-3 practices (WHO, 2020) [17,51]. The SARS-CoV-2 cytopathogenic effect is measured by its capability to infect a host cell. This is usually expressed by the tissue culture infectious dose, TCID50/mL, calculated using the method of Reed and Muench, [52], which is the viral titer at which 50% of the host cell lines are infected when inoculated in vitro with a diluted viral solution. However, because of some limitations with the in vitro tests (slow viral growth), the use of in vivo assays is taken after inoculated animals were sacrificed for within-host virus titering and pathological study [53].
Basic reproductive number is a key epidemiological factor used to measure the potential infectivity of virus-related outbreak [54,55]. It represents the average number of infected people caused by one infected individual during his/her whole contagious phase. Values of less than one means that the pandemic is most likely to stop propagating. In early stage of COVID-19 pandemic, realistic pooled values of were estimated in 29 studies, all done in China, using different mathematical methods [56]. The mean value of was evaluated as 3.38 ± 1.40 (95% confidence interval 1.9–6.49). was found to be between 2.43 to 3.10 in Italy in early stage of COVID-19 pandemic [54].
One of the key epidemiological factors in the COVID-19 pandemic is the incubation period, time elapsed between the exposure and the appearance of the first symptoms. Different pooled analysis of confirmed COVID-19 cases showed that the estimated incubation times were 5.1 days [57], 6.4 days (range 2.2–11.1) [58], and 5.0 days (range 2–14 days) [59]. Sanche and colleagues estimated, in late January 2020 in Mainland China, the average incubation period to 4.2 days. A time duration from symptoms onset to admission to hospital for treatment was estimated to 1.5 days in late January 2020 and the time from symptoms onset to death to 16.1 days [60].
Various in vitro studies showed that RNA viruses are less vulnerable to corruption due to their ability to promptly repair their genome damages by proof-reading, excision, and removing flawed RNA nucleotides that occur during their replication [61,62,63,64]. Exoribonuclease (ExoN) enzymes encoded by nsp-14 play a crucial role in maintaining the viral genome integrity [18,64,65,66]. Eckerle and workers reported that mutations in nsp-14 of SARS viruses lead to 15-fold increase in replication errors [67].
1.3. Vaccine strategy
To help prevent the spreading of the COVID-19 pandemic, most of the countries have adopted immediate measures consisting of global travel restrictions on movement, lockdowns, social distancing, patient self-isolation, and provision of medical care to infected people. Few curative methods using already known antiviral agents such as hydroxychloroquine and remdesivir were tested on patients [68,69,70]. However, results were not very encouraging for any of these agents to be considered as significant therapy yet. The best option for ending this pandemic and reestablishing a normal life remains, by far, the development of safe and effective prophylactic vaccines. This has triggered an extensive collaboration and a colossal mission between pharma companies and scientists to expedite vaccine development and production in less than a year instead of the normal 10-year period time. By the end of 2020, 259 COVID-19 vaccine projects were in the pipeline [71]. Frontrunning coronavirus vaccines, sharing the same purpose of stimulating the immune system against SARS-CoV-2, can be broadly categorized into three platforms:
the classical inactivated virus vectored vaccines based on disrupting the viral genome through chemical or physical alterations. These viruses are no longer able to replicate to cause infection, but able to trigger an immune memory response [72].
the full-length S glycoprotein- or RBD-based vaccines that generate target antigens in the infected cell [73].
the groundbreaking DNA-, mRNA-based vaccines that encode in the host cell the full-length S glycoprotein as target antigen [74].
As of 29 January 2021, five vaccines went through the necessary multiple phases of trial to ensure safety, showing more than 90% efficacy. They have been approved and licensed for use by national and international public health regulators and are being rolled out worldwide (Table 1).
Table 1.
Vaccine | Platform | Inactivation method | Developer | Reference |
---|---|---|---|---|
BNT162b2 | mRNA | — | Pfizer – BioNTech (USA, Germany) | [75,76] |
mRNA-1273 | mRNA | — | Moderna (USA) | [77,78] |
AZD1222 | Nonreplicating viral vector | Deletions in E1 and E3 genes in adenovirus vector to inhibit replications | University of Oxford AstraZeneca (UK) | [15,79,80] |
CoronaVac | Inactivated SARS-CoV-2 | β-Propiolactone to inhibit replication | Sinovac (China) | [29,81] |
Sputnik V | Heterologous recombinant adenovirus (rAd26 and rAd5) | Deletions in E1 and E3 genes in adenovirus vector to inhibit replications | Gamaleya (Russia) | [82,83] |
1.4. Different agents for SARS-CoV-2 inactivation
Virus inactivation for vaccine purposes was already known since the late 1800s [84]. In 1885, Pasteur laid the foundations of immunization with inactivated rabies virus cultured in rabbit spinal cords [85]. It was not until the discovery of the in vitro culture of viruses outside the host organism procedures that inactivated viral vaccine development was truly initiated. This allowed a large-scale production of viruses as source for inactivated vaccine purposes [86]. Vaccine producers are generally using virus growth on continuous cell lines to reduce production costs and increase vaccine safety. Once the virus has been purified, inactivation can be achieved using chemical or physical methods or a combination of the two. A wide range of chemical agents are used: ascorbic acid [87], derivatives of ethylenimine [88], and hydrogen peroxide [89]. However, formaldehyde [90] and β-propiolactone [91] are the most widely used for inactivation for decades. To avoid the extensive and time-consuming downstream processing to detoxify the virus cultures from chemical inactivators, the use of γ‐irradiation as a physical alternative method to chemical inactivation has been proposed by many authors. Preparation of experimental vaccines against several viral diseases using γ‐irradiation is reported in the literature: bluetongue [92], Venezuelan equine encephalitis [93], rabies [94], smallpox [95], influenza [96], HIV [97], Ebola [98], rotavirus [99], and polio [100].
The choice of an inactivation method preserving the viral epitope integrity is important since the damage of the envelop protein will lessen the efficacy of the vaccine [101]. Several studies showed that viral inactivation by formaldehyde, hydrogen peroxide, or binary ethylenimine derivatives is nonselective and can damage the envelope protein leading to a poor immune response [102,103]. Nevertheless, γ-irradiation has shown a superior inactivation method by preserving the viral antigens intact to trigger the immunogenicity while destroying nucleic acids to inhibit the viral replication in human cells [104,105]. This advantageous attribute of γ-irradiation can be ascribed to its high penetration depth that causes direct damage to nucleic acids without altering structural proteins [96,106,107].
Due to the potentially dangerous consequences of SARS-CoV-2 human infection, extreme attention should be paid to ensure that inactivation procedures are efficient. Effective inactivation of the SARS-CoV-2 is vital as it allows research, especially the development of new vaccines, to be conducted under safe conditions [108]. Various methods are already available for SARS-CoV effective inactivation [109] and could be tested on SARS-CoV-2 since these two viruses share a great deal of genome: ultraviolet radiation, thermal treatment, extreme pH values, and commonly used disinfectants offer an effective virus inactivation. Duan and colleagues reported an inactivation of SARS-CoV virus after 15 min exposure to ultraviolet C, whereas ultraviolet A and B had no effect on its viability, irrespective of the duration of the exposure [110]. Heat can denature SARS-CoV secondary structural proteins. A complete inactivation of this virus at 75°C for 45 min was reported by Darnell and colleagues [111]. For inactivation with detergents, Gerlach et al. showed that SARS-CoV-2 can be efficiently inactivated by 70% ethanol, 0.1% hydrogen peroxide, and 0.1% sodium sulphate, commonly available in hand soaps, within 60 s of exposure on various surfaces [112]. pH has a great effect on the viability of SARS-CoV-2. Chan et al. reported that the virus survived for up to 6 days in a medium with pH range [5–9], but lost between 2.9 and 5.33 log10 infectivity. At pH 4 and pH 11, it remained viable for 1–2 days. At extreme pHs (pH 2–3 and pH 11–12), the virus lost 5.25 log10 infectivity within only 1 day [16].
In this perspective, γ-inactivation of viruses could be an important and promising tool for SARS-CoV-2 vaccine development (Figure 1). In this review, we analyze the potential use of γ-irradiation to inactivate the SARS-CoV-2 by altering its genetic material while preserving its structural proteins.
1.5. Radiolysis of water in biological matter: mechanisms of radiobiological action
The two major processes in the interaction of energetic photons or charged particles with aqueous biological medium are ionization and excitation of water molecules and biologically important macromolecules such as DNA, RNA, lipids, and proteins [113,114]. The electrons liberated in the ionization have enough energy to ionize further molecules in a manner that energy is deposited in spurs. When their energy falls below the ionization threshold of water, the electrons become solvated . Excited water molecules can dissociate into free radicals and . These physicochemical processes, concentrated in tracks along the path of the ionizing species, are complete approximately 10−12 s after the absorption of the ionizing radiation [115,116]. The radiolysis products either react with each other within the spurs to produce reactive oxygen species (ROS), such as superoxide radical O2 •− and its conjugate perhydroxyl radical HO2 •, or diffuse homogeneously into the bulk of the biological medium where they are scavenged by biological macromolecules. The spur diffusion is complete approximately 10−7 s after the absorption of the ionizing radiation [117].
1.6. Mechanism of viral inactivation
γ-irradiation disrupts viruses by altering mainly their RNA genetic material. The number of nitrogenous bases and their sequence in the RNA is crucial for determining the viral sensitivity towards γ-irradiation. The more target nucleotides, the more likely the nucleic acid genome will be damaged for a given absorbed dose [118]. The mechanism behind this damage falls into two types: direct and indirect. Direct damage is caused by the radiation-induced cleavage of the sugar-phosphate backbone or the cross-linking, deletion, substitution, and insertion in the sequence of nitrogen bases [119,120]. Indirect damage is attributed to the oxidative stress of the radiolytically produced ROS on the viral material, leading to its fragmentation and cross-linking [121,122]. A minimum energy deposition of 17.5 eV within a critical distance of 6 Å from the nucleotide (corresponding to a sensitive spherical volume of 0.596 nm3) can induce a lethal damage to the viral RNA [123]. Disruption to the protein capsid and the lipid bilayer envelope, by lipid and protein peroxidation chain reactions, may as well result in the reduction of viral pathogenicity [70,124,125]. It has been reported that, for viruses belonging to the enveloped Coronaviridae family, the conformational changes in the spike glycoprotein S block the viral binding to the host cell plasma membrane and prevent cellular internalization, the first stage in viral infection [111,126]. Studies suggested that genetic material rather than protein and lipid envelopes is likely to be the primary target for viral inactivation [107,127]. Nims et al. reported that the presence or absence of a viral envelope does not seem to be a major factor of inactivation by γ-irradiation [128].
Single-strand break (for single-stranded viruses) and double-strand break (for double-stranded viruses) are generally sufficient to inactivate the viral genome [129]. Based on the hypothesis of the single-hit-single-target (SHST) model [130,131], the inactivation of viruses is typically expressed by the following relationship [132]:
(1) |
where and are the virus population before and after the irradiation, respectively, being the radiation dose. depicts the required irradiation dose to reduce the initial virus titer by 90% (or reduce the population by a factor of 10). values vary between different types of viruses mainly due to the significant differences in their genome, capsid morphology, and the presence or absence of an envelope. For convenience, the viral inactivation is expressed in terms of log10 reduction, which is the logarithm base 10 of the ratio of the viral titer before and after the inactivation:
(2) |
It should be noted that corresponds to . For instance, corresponds to 90% reduction (or 10-fold) and corresponds to 99% reduction (or 100-fold).
Feldmann and colleagues showed that the inactivation was inversely correlated with genome size [133]. They measured the radiation doses for a 6 log10 reduction and found 2 Mrads for coronaviruses (∼29 kb genome size), 4 Mrads for filoviruses (∼19 kb), 8 Mrads for arenaviruses, bunyaviruses, orthomyxoviruses, and paramyxoviruses (∼13 kb) and 10 Mrads for flaviviruses (∼9 kb). Viruses having single-strand nucleic acid present the highest radiosensitivity. Hume and colleagues [127] reported that the three enveloped single-stranded RNA viruses of similar sizes, namely morbillivirus (90–150 nm), bunyavirus (90–120 nm), and rhabdovirus (70–150 nm), showed a comparable D 10 values (2.53, 2.61, and 2.71 kGy respectively) when irradiated under the same experimental protocol.
Leung and workers cultured SARS-CoV-2 on Vero cells in the presence of 1% fetal bovine serum and 1% l-glutamine. Virus-containing supernatants were titered after irradiation [134]. The D 10 was 1.6 kGy and the complete inactivation of the SARS-CoV-2 was attained with an absorbed dose of 10 kGy, value lower than the 20 kGy previously reported value for the similar SARS-CoV [133]. Even though the single-stranded RNA viruses may present a certain radioresistance, Nims and colleagues showed that no strong clue can explain the discrepancies in the log10 values for virus inactivation by γ-irradiation, as shown in Table 2 [135]. Multiple causative parameters may be involved in this discrepancy, including, but not limited to, sera matrices preparation variability from sample-to-sample, variability in γ-irradiation procedures (dose rate), and variability in the purity of the virus stock quality.
Table 2.
Virus | Family | Morphology (not to scale) | Size (nm) | Genome size (kb) * | Nucleic acid genome | D 10 (kGy) | log10 reduction/kGy c | References |
---|---|---|---|---|---|---|---|---|
IBRb | Herpesviridae | 100–120 | 120–230 | Double-stranded DNA | 3.22 | 0.310 | [136,137] | |
APV | Poxviridae | 240–300 | 130–260 | Double-stranded DNA | 2.20 | 0.456 | [138,139] | |
PI3b | Paramyxoviridae | 100–200 | 13–19 | Single-stranded RNA | 4.78 | 0.209 | [128,140] | |
BVDVa | Flaviviridae | 50–70 | 9–13 | Single-stranded RNA | 5.05 | 0.198 | [141,142] | |
SARS-CoV-2 | Coronaviridae | 20–25 | 26–32 | Single-stranded RNA | 1.60 | 0.625 | [134,143] | |
BEFVa | Rhabdoviridae | 75 × 150 | 10–16 | Single-stranded RNA | 2.94 | 0.340 | [142,144] | |
Akabanea | Bunyavuridae | 80–120 | 11–23 | Single-stranded RNA | 2.50 | 0.400 | [142,145] | |
Ainoa | Bunyavuridae | 80–120 | 11–23 | Single-stranded RNA | 3.45 | 0.290 | [142,146] |
APV: avian poxvirus, PI3: parainfluenza virus type 3, IBR: infectious bovine rhinotracheitis, BVDV: bovine viral diarrhea virus, BEFV: bovine ephemeral fever virus.
A kilobase (kb) pair is a unit of genome size measurement equal to 1,000 base pairs of DNA or RNA.
Viruses in bovine serum.
Viruses spiked into fetal bovine serum.
log10 reduction per kGy represents the slope of the viral inactivation (log10 reduction in titer) vs radiation dose in kGy.
In another study, Schmidt and workers [132] investigated the fractionated and continuous electron beam irradiation of four different types of viruses: the Human Immunodeficiency Virus-2 (Retroviridae enveloped HIV-2), the Hepatovirus A (Picornaviridae non-enveloped HAV), the Pseudorabies Virus (Herpesviridae, enveloped PRV), and the Porcine Parvovirus (Parvoviridae non-enveloped PPV). The cell lines for these viruses were respectively human T lymphocyte cells, mink-lung cells, embryonal rhesus monkey kidney cells, and pig kidney cells. The irradiation doses for the continuous beam were multiple of 3.4 kGy and up to 34 kGy, while for the fractionated beam, a dose of 3.4 Gy was applied up to 10 times. The values were estimated from the regression curve TCID50/mL vs absorbed dose. Except for PRV, each type of virus showed a slightly greater radioresistance in continuous than fractionated irradiation. This might be explained by the ability of the viruses to repair their sublethal damages to their viral genome between two successive fractions. The least resistant was the PRV (continuous beam: 5.6 kGy, fractionated beam: 5.8 kGy) and the most resistant was the HIV-2 (continuous beam: 9 kGy, fractionated beam: 8 kGy).
The presence of solutes in the irradiation culture of viruses renders the radiation-induced inactivation of viruses less efficient. de Roda Husman et al. [125] compared the inactivation of the respiratory feline calicivirus (FeCV) and the enteric canine calicivirus (CaCV) with the Escherichia bacteriophage MS2 in viral culture of different protein concentration. They reported a reduction factor at a dose of ∼120 Gy when γ-irradiating MS2 in tap water or in low-protein-contents. They obtained doses of 500 and 300 Gy, for a 3 log10 reductions factors, for FeCV and CaCV, respectively, in low-protein-content cultures. No or very little inactivation was observed when MS2, FeCV, and CaCV were γ-irradiated in high-protein-content culture. The presence of OH˙ and H˙ scavengers, such as proteins, lipids, etc., significantly reduces the viral inactivation. The authors also reported that FeCV and CaCV showed a second-order kinetics, with faster inactivation happening at doses between 0 and 400 Gy and slower inactivation happening at doses from 400 to 800 Gy.
2. Conclusion
The eruption of the SARS-CoV-2 new virus poses a real challenge and worries in a sense that its attributes are initially unknown and very limited viral data on COVID-19 infection is currently available. The virus is still infecting populations globally. Previous studies from other viruses and particularly the SARS-CoV and MERS-CoV have showed that damaging the genetic material can destroy infectivity while retaining immunogenicity. This review showed that ionizing radiation can potentially inactivate almost all the RNA viruses, by disrupting their genomic material. This could suggest a basis for developing a potential γ-inactivated virus-based vaccine against the spread of the COVID-19 pandemic. Improving its immunogenicity and preventing any potential undesired effects that could compromise the safety of the vaccine are of course other important factors which should also be taken into full consideration and thoroughly examined.
Acknowledgments
The authors gratefully acknowledge Deanship of Scientific Research at King Abdulaziz University for technical and financial support
Footnotes
Funding information: This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. RG-6-135-40.
Conflict of interest: The authors state no conflict of interest.
Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
References
- [1].Mäntynen S, Sundberg L-R, Oksanen H, Poranen M. Half a century of research on membrane-containing bacteriophages: bringing new concepts to modern virology. Viruses [Internet]. 2019 Jan 18;11(1):76. Available from: http://www.mdpi.com/1999-4915/11/1/76 [DOI] [PMC free article] [PubMed]; Mäntynen S, Sundberg L-R, Oksanen H, Poranen M. Half a century of research on membrane-containing bacteriophages: bringing new concepts to modern virology. Viruses [Internet] 2019 Jan 18;11(1):76. doi: 10.3390/v11010076. http://www.mdpi.com/1999-4915/11/1/76 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [2].Menéndez-Arias L, Andino R. Viral polymerases. Virus Res [Internet]. 2017 Apr;234:1–3. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0168170217301284 [DOI] [PMC free article] [PubMed]; Menéndez-Arias L, Andino R. Viral polymerases. Virus Res [Internet] 2017 Apr;234:1–3. doi: 10.1016/j.virusres.2017.02.003. https://linkinghub.elsevier.com/retrieve/pii/S0168170217301284 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Islam MR, Hoque MN, Rahman MS, Alam ASMRU, Akther M, Puspo JA, et al. Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity. Sci Rep [Internet]. 2020 Dec 1 [cited 2021 Mar 11];10(1):14004. Available from: https://doi.org/10.1038/s41598-020-70812-6; Islam MR, Hoque MN, Rahman MS, Alam ASMRU, Akther M, Puspo JA. et al. Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity. Sci Rep [Internet] 2020 Dec 1 [cited 2021 Mar 11];10(1):14004. doi: 10.1038/s41598-020-70812-6. . Available from: [DOI] [Google Scholar]
- [4].Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P, et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med [Internet]. 2020 Apr 22 [cited 2021 Mar 11];18(1):1–9. Available from: https://pubmed.ncbi.nlm.nih.gov/32321524/ [DOI] [PMC free article] [PubMed]; Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P. et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med [Internet] 2020 Apr 22 [cited 2021 Mar 11];18(1):1–9. doi: 10.1186/s12967-020-02344-6. https://pubmed.ncbi.nlm.nih.gov/32321524/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Servín-Blanco R, Zamora-Alvarado R, Gevorkian G, Manoutcharian K. Antigenic variability: obstacles on the road to vaccines against traditionally difficult targets. Hum Vaccin Immunother [Internet]. 2016 Oct 2;12(10):2640–8. Available from: https://www.tandfonline.com/doi/full/10.1080/21645515.2016.1191718 [DOI] [PMC free article] [PubMed]; Servín-Blanco R, Zamora-Alvarado R, Gevorkian G, Manoutcharian K. Antigenic variability: obstacles on the road to vaccines against traditionally difficult targets. Hum Vaccin Immunother [Internet] 2016 Oct 2;12(10):2640–8. doi: 10.1080/21645515.2016.1191718. https://www.tandfonline.com/doi/full/10.1080/21645515.2016.1191718 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Carlson JM, Le AQ, Shahid A, Brumme ZL. HIV-1 adaptation to HLA: a window into virus–host immune interactions. Trends Microbiol [Internet]. 2015 Apr;23(4):212–24. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0966842X14002650 [DOI] [PubMed]; Carlson JM, Le AQ, Shahid A, Brumme ZL. HIV-1 adaptation to HLA: a window into virus–host immune interactions. Trends Microbiol [Internet] 2015 Apr;23(4):212–24. doi: 10.1016/j.tim.2014.12.008. https://linkinghub.elsevier.com/retrieve/pii/S0966842X14002650 . Available from: [DOI] [PubMed] [Google Scholar]
- [7].Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953–66. [DOI] [PubMed]; Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S. et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953–66. doi: 10.1056/NEJMoa030781. [DOI] [PubMed] [Google Scholar]
- [8].Cheng VCC, Lau SKP, Woo PCY, Yuen Y. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev [Internet]. 2007 [cited 2020 Aug 9];20(4):660–94. Available from: http://cmr.asm.org/ [DOI] [PMC free article] [PubMed]; Cheng VCC, Lau SKP, Woo PCY, Yuen Y. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev [Internet] 2007 [cited 2020 Aug 9];20(4):660–94. doi: 10.1128/CMR.00023-07. http://cmr.asm.org/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med [Internet]. 2012 Nov 8;367(19):1814–20. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1211721 [DOI] [PubMed]; Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med [Internet] 2012 Nov 8;367(19):1814–20. doi: 10.1056/NEJMoa1211721. http://www.nejm.org/doi/abs/10.1056/NEJMoa1211721 . Available from: [DOI] [PubMed] [Google Scholar]
- [10].Chan JFW, Yuan S, Kok KH, To KKW, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet [Internet]. 2020 Feb;39;5(10223):514–23. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673620301549 [DOI] [PMC free article] [PubMed]; Chan JFW, Yuan S, Kok KH, To KKW, Chu H, Yang J. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet [Internet] 2020 Feb;39;5(10223):514–23. doi: 10.1016/S0140-6736(20)30154-9. https://linkinghub.elsevier.com/retrieve/pii/S0140673620301549 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Lun Z-R, Qu L-H. Animal-to-human SARS-associated coronavirus transmission? Emerg Infect Dis [Internet]. 2004 May;10(5):959. Available from: http://wwwnc.cdc.gov/eid/article/10/5/04-0022_article.htm [DOI] [PMC free article] [PubMed]; Lun Z-R, Qu L-H. Animal-to-human SARS-associated coronavirus transmission? Emerg Infect Dis [Internet] 2004 May;10(5):959. doi: 10.3201/eid1005.040022. http://wwwnc.cdc.gov/eid/article/10/5/04-0022_article.htm . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, et al. Severe acute respiratory syndrome-related coronavirus: the species and its viruses-a statement of the coronavirus study group; 2020 [cited 2020 Aug 12];1:1–20. Available from: https://doi.org/10.1101/2020.02.07.937862; Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA. et al. Severe acute respiratory syndrome-related coronavirus: the species and its viruses-a statement of the coronavirus study group. 2020 [cited 2020 Aug 12];1:1–20. doi: 10.1101/2020.02.07.937862. . Available from: [DOI] [Google Scholar]
- [13].Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. [DOI] [PMC free article] [PubMed]; Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, et al. SARS-CoV-2, SARS-CoV, and MERS-CoV: a comparative overview. Infez Med. 2020;28(2):174–84. [PubMed]; Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS. et al. SARS-CoV-2, SARS-CoV, and MERS-CoV: a comparative overview. Infez Med. 2020;28(2):174–84. [PubMed] [Google Scholar]
- [15].Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet [Internet]. 2020 Dec 19 [cited 2021 Feb 11];396(10267):1979–93. [DOI] [PMC free article] [PubMed]; Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR. et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet [Internet] 2020 Dec 19 [cited 2021 Feb 11];396(10267):1979–93. doi: 10.1016/S0140-6736(20)32466-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Chan KH, Sridhar S, Zhang RR, Chu H, Fung AYF, Chan G, et al. Factors affecting stability and infectivity of SARS-CoV-2. J Hosp Infect. 2020 Oct 1;106(2):226–31. [DOI] [PMC free article] [PubMed]; Chan KH, Sridhar S, Zhang RR, Chu H, Fung AYF, Chan G. et al. Factors affecting stability and infectivity of SARS-CoV-2. J Hosp Infect. 2020 Oct 1;106(2):226–31. doi: 10.1016/j.jhin.2020.07.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].WHO. WHO coronavirus disease (COVID-19) dashboard. Geneva: World Health Organization; 2020.; WHO. WHO coronavirus disease (COVID-19) dashboard. Geneva: World Health Organization; 2020. [Google Scholar]
- [18].Ojha R, Gupta N, Naik B, Singh S, Verma VK, Prusty D, et al. High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19. Eur J Pharm Sci [Internet]. 2020 Aug 1 [cited 2021 Feb 11];151:105375. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224663/ [DOI] [PMC free article] [PubMed]; Ojha R, Gupta N, Naik B, Singh S, Verma VK, Prusty D. et al. High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19. Eur J Pharm Sci [Internet] 2020 Aug 1 [cited 2021 Feb 11];151:105375. doi: 10.1016/j.ejps.2020.105375. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224663/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China Supplemental content. JAMA Cardiol [Internet]. 2020 [cited 2020 Aug 9];5(7):802–10. Available from: https://jamanetwork.com/ [DOI] [PMC free article] [PubMed]; Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China Supplemental content. JAMA Cardiol [Internet] 2020 [cited 2020 Aug 9];5(7):802–10. doi: 10.1001/jamacardio.2020.0950. https://jamanetwork.com/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, et al. Comorbidity and its impact on patients with COVID-19. SN Compr Clin Med [Internet]. 2020 Aug 25;2(8):1069–76. Available from: http://link.springer.com/10.1007/s42399-020-00363-4 [DOI] [PMC free article] [PubMed]; Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P. et al. Comorbidity and its impact on patients with COVID-19. SN Compr Clin Med [Internet] 2020 Aug 25;2(8):1069–76. doi: 10.1007/s42399-020-00363-4. http://link.springer.com/10.1007/s42399-020-00363-4 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis [Internet]; 2020 [cited 2020 Aug 9]. Available from: https://www.sciencedirect.com/science/article/pii/S1201971220301363; Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Int J Infect Dis [Internet] 2020 [cited 2020 Aug 9]. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis.https://www.sciencedirect.com/science/article/pii/S1201971220301363 . Available from: [Google Scholar]
- [22].Hassan SA, Sheikh FN, Jamal S, Ezeh JK, Akhtar A. Coronavirus (COVID-19): a review of clinical features, diagnosis, and treatment. Cureus. 2020 Mar 21;12:1–7. [DOI] [PMC free article] [PubMed]; Hassan SA, Sheikh FN, Jamal S, Ezeh JK, Akhtar A. Coronavirus (COVID-19): a review of clinical features, diagnosis, and treatment. Cureus. 2020 Mar 21;12:1–7. doi: 10.7759/cureus.7355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [23].Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020 Mar 12;579(7798):265–9. [DOI] [PMC free article] [PubMed]; Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG. et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020 Mar 12;579(7798):265–9. doi: 10.1038/s41586-020-2008-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Luan J, Lu Y, Jin X. Research LZ-B and biophysical, 2020 U. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Commun. 2020 May 21;526(1):165–9. [DOI] [PMC free article] [PubMed]; Luan J, Lu Y, Jin X. Research LZ-B and biophysical, 2020 U. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Commun. 2020 May 21;526(1):165–9. doi: 10.1016/j.bbrc.2020.03.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Tortorici MA, Veesler D. Structural insights into coronavirus entry. Adv Virus Res. 2019;105:93–116. 10.1016/bs.aivir.2019.08.002. [DOI] [PMC free article] [PubMed]; Tortorici MA, Veesler D. Structural insights into coronavirus entry. Adv Virus Res. 2019;105:93–116. doi: 10.1016/bs.aivir.2019.08.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Raj R. Analysis of non-structural proteins, NSPs of SARS-CoV-2 as targets for computational drug designing. Biochem Biophys Rep [Internet]. 2021 Mar [cited 2021 Mar 11];25:100847. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750489/ [DOI] [PMC free article] [PubMed]; Raj R. Analysis of non-structural proteins, NSPs of SARS-CoV-2 as targets for computational drug designing. Biochem Biophys Rep [Internet] 2021 Mar [cited 2021 Mar 11];25:100847. doi: 10.1016/j.bbrep.2020.100847. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750489/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [27].Silva SJR, Alves da Silva CT, Mendes RPG, Pena L. Role of nonstructural proteins in the pathogenesis of SARS‐CoV‐2. J Med Virol [Internet]. 2020 Sep 2 [cited 2021 Mar 11];92(9):1427–9. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25858 [DOI] [PMC free article] [PubMed]; Silva SJR, Alves da Silva CT, Mendes RPG, Pena L. Role of nonstructural proteins in the pathogenesis of SARS‐CoV‐2. J Med Virol [Internet] 2020 Sep 2 [cited 2021 Mar 11];92(9):1427–9. doi: 10.1002/jmv.25858. https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25858 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [28].Clark LK, Green TJ, Petit CM. Structure of nonstructural protein 1 from SARS-CoV-2. J Virol [Internet]. 2020 Nov 24 [cited 2021 Mar 11];95(4):1–12. Available from: http://jvi.asm.org/ [DOI] [PMC free article] [PubMed]; Clark LK, Green TJ, Petit CM. Structure of nonstructural protein 1 from SARS-CoV-2. J Virol [Internet] 2020 Nov 24 [cited 2021 Mar 11];95(4):1–12. doi: 10.1128/JVI.02019-20. http://jvi.asm.org/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science (80) [Internet]. 2020 May 15 [cited 2021 Mar 11];368(6492):779–82. Available from: https://pubmed.ncbi.nlm.nih.gov/32277040/ [DOI] [PMC free article] [PubMed]; Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L. et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science (80) [Internet] 2020 May 15 [cited 2021 Mar 11];368(6492):779–82. doi: 10.1126/science.abb7498. https://pubmed.ncbi.nlm.nih.gov/32277040/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci [Internet]. 2020 Mar 21;63(3):457–60. Available from: http://link.springer.com/10.1007/s11427-020-1637-5 [DOI] [PMC free article] [PubMed]; Xu X, Chen P, Wang J, Feng J, Zhou H, Li X. et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci [Internet] 2020 Mar 21;63(3):457–60. doi: 10.1007/s11427-020-1637-5. http://link.springer.com/10.1007/s11427-020-1637-5 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [31].Yao M, Zhang L, Ma J, Zhou L. On airborne transmission and control of SARS-Cov-2. Sci Total Environ [Internet]. 2020 Aug;731:139178. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0048969720326954 [DOI] [PMC free article] [PubMed]; Yao M, Zhang L, Ma J, Zhou L. On airborne transmission and control of SARS-Cov-2. Sci Total Environ [Internet] 2020 Aug;731:139178. doi: 10.1016/j.scitotenv.2020.139178. https://linkinghub.elsevier.com/retrieve/pii/S0048969720326954 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [32].Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. In: Gallagher T, editor. J Virol [Internet]. 2020 Jan 29;94(7):1–25. Available from: https://jvi.asm.org/content/94/7/e00127-20 [DOI] [PMC free article] [PubMed]; Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. In: Gallagher T, editor. J Virol [Internet] 2020 Jan 29;94(7):1–25. doi: 10.1128/JVI.00127-20. https://jvi.asm.org/content/94/7/e00127-20 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].Yang X-H, Deng W, Tong Z, Liu Y-X, Zhang L-F, Zhu H, et al. Comparative medicine mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus Infection [Internet]. ingentaconnect.com; 2007 [cited 2020 Aug 9]. Available from: https://www.ingentaconnect.com/content/aalas/cm/2007/00000057/00000005/art00003 [PubMed]; Yang X-H, Deng W, Tong Z, Liu Y-X, Zhang L-F, Zhu H, ingentaconnect.com. 2007 [cited 2020 Aug 9]. Comparative medicine mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus Infection [Internet]https://www.ingentaconnect.com/content/aalas/cm/2007/00000057/00000005/art00003 . Available from: [PubMed] [Google Scholar]
- [34].Devaux CA, Rolain J-M, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect [Internet]. 2020 Jun;53(3):425–35. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1684118220301092 [DOI] [PMC free article] [PubMed]; Devaux CA, Rolain J-M, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect [Internet] 2020 Jun;53(3):425–35. doi: 10.1016/j.jmii.2020.04.015. https://linkinghub.elsevier.com/retrieve/pii/S1684118220301092 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. Mass Med Soc [Internet]. [cited 2020 Aug 9];382:1199–207. Available from: https://www.nejm.org/doi/full/10.1056/NEJMOa2001316 [DOI] [PMC free article] [PubMed]; Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. Mass Med Soc [Internet] [cited 2020 Aug 9];382:1199–207. doi: 10.1056/NEJMoa2001316. https://www.nejm.org/doi/full/10.1056/NEJMOa2001316 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36].Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. New Engl J Med. 2020;382:1199–207. [DOI] [PMC free article] [PubMed]; Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. New Engl J Med. 2020;382:1199–207. doi: 10.1056/NEJMoa2001316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [37].Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor. naturecom [Internet]. 2020 [cited 2020 Aug 12]. Available from: https://www.nature.com/articles/s41423-020-0400-4?report=reader [DOI] [PMC free article] [PubMed]; Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor. naturecom [Internet] 2020 [cited 2020 Aug 12] doi: 10.1038/s41423-020-0400-4. https://www.nature.com/articles/s41423-020-0400-4?report=reader . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [38].Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020 May 14;581(7807):221–4. [DOI] [PMC free article] [PubMed]; Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020 May 14;581(7807):221–4. doi: 10.1038/s41586-020-2179-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [39].Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Int Med. 2020;76:14–20. [DOI] [PMC free article] [PubMed]; Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Int Med. 2020;76:14–20. doi: 10.1016/j.ejim.2020.04.037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [40].Grove J, Marsh M. The cell biology of receptor-mediated virus entry. J Cell Biol. 2011;195:1071–82. [DOI] [PMC free article] [PubMed]; Grove J, Marsh M. The cell biology of receptor-mediated virus entry. J Cell Biol. 2011;195:1071–82. doi: 10.1083/jcb.201108131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020 Apr 16;181(2):281–92. [DOI] [PMC free article] [PubMed]; Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020 Apr 16;181(2):281–92. doi: 10.1016/j.cell.2020.02.058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [42].Sullivan CS, Ganem D. microRNAs and viral infection. Mol Cell. 2005;20(1):3–7. [DOI] [PubMed]; Sullivan CS, Ganem D. microRNAs and viral infection. Mol Cell. 2005;20(1):3–7. doi: 10.1016/j.molcel.2005.09.012. [DOI] [PubMed] [Google Scholar]
- [43].South AM, Diz DI, Chappell MC. COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Circ Physiol. 2020;318:1084–90. [DOI] [PMC free article] [PubMed]; South AM, Diz DI, Chappell MC. COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Circ Physiol. 2020;318:1084–90. doi: 10.1152/ajpheart.00217.2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [44].Liu J, Liao X, Qian S, Yuan J, Wang F, Liu Y, et al. Community transmission of severe acute respiratory syndrome coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis. 2020 Jun;26(6):1320–23. 10.3201/eid2606.200239. [DOI] [PMC free article] [PubMed]; Liu J, Liao X, Qian S, Yuan J, Wang F, Liu Y. et al. Community transmission of severe acute respiratory syndrome coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis. 2020 Jun;26(6):1320–23. doi: 10.3201/eid2606.200239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [45].Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;395:1137–44. [DOI] [PMC free article] [PubMed]; Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K. et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;395:1137–44. doi: 10.1016/S0140-6736(20)30607-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [46].Lu J, Gu J, Li K, Xu C, Su W, Lai Z, et al. Early release-COVID-19 outbreak associated with air conditioning in restaurant, Guangzhou, China, 2020; 2020. [DOI] [PMC free article] [PubMed]; Lu J, Gu J, Li K, Xu C, Su W, Lai Z, Early release-COVID-19 outbreak associated with air conditioning in restaurant, Guangzhou, China, 2020. 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [47].Frontera A, Martin C, Vlachos K, Sgubin G. Regional air pollution persistence links to covid19 infection zoning. J Infect. 2020;81:318–56. [DOI] [PMC free article] [PubMed]; Frontera A, Martin C, Vlachos K, Sgubin G. Regional air pollution persistence links to covid19 infection zoning. J Infect. 2020;81:318–56. doi: 10.1016/j.jinf.2020.03.045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [48].Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Environ Int [Internet]. 2020 Jun;139:105730. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016041202031254X [DOI] [PMC free article] [PubMed]; Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Environ Int [Internet] 2020 Jun;139:105730. doi: 10.1016/j.envint.2020.105730. https://linkinghub.elsevier.com/retrieve/pii/S016041202031254X . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [49].Chia PY, Coleman KK, Tan YK, Ong SWX, Gum M, Lau SK, et al. Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients. Nat Commun [Internet]. 2020 Dec 29;11(1):2800. Available from: http://www.nature.com/articles/s41467-020-16670-2 [DOI] [PMC free article] [PubMed]; Chia PY, Coleman KK, Tan YK, Ong SWX, Gum M, Lau SK. et al. Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients. Nat Commun [Internet] 2020 Dec 29;11(1):2800. doi: 10.1038/s41467-020-16670-2. http://www.nature.com/articles/s41467-020-16670-2 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [50].Guo Z-D, Wang Z-Y, Zhang S-F, Li X, Li L, Li C, et al. Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020. Emerg Infect Dis. 2020;26(7):10–3201. [DOI] [PMC free article] [PubMed]; Guo Z-D, Wang Z-Y, Zhang S-F, Li X, Li L, Li C. et al. Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020. Emerg Infect Dis. 2020;26(7):10–3201. doi: 10.3201/eid2607.200885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [51].WHO. WHO-I guidance. Laboratory biosafety guidance related to the novel coronavirus (2019-nCoV). Geneva: World Health Organization; 2020.; WHO. WHO-I guidance. Laboratory biosafety guidance related to the novel coronavirus (2019-nCoV) Geneva: World Health Organization; 2020. [Google Scholar]
- [52].Ramakrishnan MA. Determination of 50% endpoint titer using a simple formula. Artic World J Virol [Internet]. 2016 [cited 2020 Aug 12];5(2):85. Available from: http://dx.doi.org/10.5501/wjv.v5.i2.85 [DOI] [PMC free article] [PubMed]; Ramakrishnan MA. Determination of 50% endpoint titer using a simple formula. Artic World J Virol [Internet] 2016 [cited 2020 Aug 12];5(2):85. doi: 10.5501/wjv.v5.i2.85. . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [53].Gombold J, Karakasidis S, Niksa P, Podczasy J, Neumann K, Richardson J, et al. Systematic evaluation of in vitro and in vivo adventitious virus assays for the detection of viral contamination of cell banks and biological products. Vaccine [Internet]. 2014 May 19 [cited 2021 Mar 11];32(24):2916–26. Available from: https://pubmed.ncbi.nlm.nih.gov/24681273/ [DOI] [PMC free article] [PubMed]; Gombold J, Karakasidis S, Niksa P, Podczasy J, Neumann K, Richardson J. et al. Systematic evaluation of in vitro and in vivo adventitious virus assays for the detection of viral contamination of cell banks and biological products. Vaccine [Internet] 2014 May 19 [cited 2021 Mar 11];32(24):2916–26. doi: 10.1016/j.vaccine.2014.02.021. https://pubmed.ncbi.nlm.nih.gov/24681273/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [54].D’Arienzo M, Coniglio A. Assessment of the SARS-CoV-2 basic reproduction number, R0, based on the early phase of COVID-19 outbreak in Italy. Biosaf Heal. 2020;2:57–9. [DOI] [PMC free article] [PubMed]; D’Arienzo M, Coniglio A. Assessment of the SARS-CoV-2 basic reproduction number, R0, based on the early phase of COVID-19 outbreak in Italy. Biosaf Heal. 2020;2:57–9. doi: 10.1016/j.bsheal.2020.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [55].Fanelli D, Piazza F. Analysis and forecast of COVID-19 spreading in China, Italy and France. Chaos Solitons Fractals [Internet]. 2020 May;134:109761. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0960077920301636 [DOI] [PMC free article] [PubMed]; Fanelli D, Piazza F. Analysis and forecast of COVID-19 spreading in China, Italy and France. Chaos Solitons Fractals [Internet] 2020 May;134:109761. doi: 10.1016/j.chaos.2020.109761. https://linkinghub.elsevier.com/retrieve/pii/S0960077920301636 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [56].Alimohamadi Y, Taghdir M, Sepandi M. Estimate of the basic reproduction number for COVID-19: a systematic review and meta-analysis. J Prev Med Public Heal [Internet]. 2020 May 31;53(3):151–7. Available from: http://jpmph.org/journal/view.php?doi=10.3961/jpmph.20.076 [DOI] [PMC free article] [PubMed]; Alimohamadi Y, Taghdir M, Sepandi M. Estimate of the basic reproduction number for COVID-19: a systematic review and meta-analysis. J Prev Med Public Heal [Internet] 2020 May 31;53(3):151–7. doi: 10.3961/jpmph.20.076. http://jpmph.org/journal/view.php?doi=10.3961/jpmph.20.076 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [57].Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med [Internet]. 2020 May 5;172(9):577–82. Available from: https://www.acpjournals.org/doi/10.7326/M20-0504 [DOI] [PMC free article] [PubMed]; Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR. et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med [Internet] 2020 May 5;172(9):577–82. doi: 10.7326/M20-0504. https://www.acpjournals.org/doi/10.7326/M20-0504 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [58].Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019- nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill. 2020;25(5):pii=2000062. [DOI] [PMC free article] [PubMed]; Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019- nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill. 2020;25(5):pii=2000062. doi: 10.2807/1560-7917.ES.2020.25.5.2000062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [59].Linton NM, Kobayashi T, Yang Y, Hayashi K, Akhmetzhanov AR, Jung S-M, et al. Clinical medicine incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: a statistical analysis of publicly available case data. mdpi.com [Internet]; 2020 [cited 2020 Aug 9];538:1–9. Available from: www.mdpi.com/journal/jcm [DOI] [PMC free article] [PubMed]; Linton NM, Kobayashi T, Yang Y, Hayashi K, Akhmetzhanov AR, Jung S-M. et al. Clinical medicine incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: a statistical analysis of publicly available case data. mdpi.com [Internet] 2020 [cited 2020 Aug 9];538:1–9. doi: 10.3390/jcm9020538. www.mdpi.com/journal/jcm . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [60].Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis [Internet]. 2020 Jul;26(7):1470–7. Available from: http://wwwnc.cdc.gov/eid/article/26/7/20-0282_article.htm [DOI] [PMC free article] [PubMed]; Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis [Internet] 2020 Jul;26(7):1470–7. doi: 10.3201/eid2607.200282. http://wwwnc.cdc.gov/eid/article/26/7/20-0282_article.htm . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [61].Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, et al. Discovery of an RNA virus 3′ → 5′ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci USA [Internet]. 2006 Mar 28 [cited 2021 Feb 11];103(13):5108–13. Available from: www.pnas.orgcgidoi10.1073pnas.0508200103 [DOI] [PMC free article] [PubMed]; Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B. et al. Discovery of an RNA virus 3′ → 5′ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci USA [Internet] 2006 Mar 28 [cited 2021 Feb 11];103(13):5108–13. doi: 10.1073/pnas.0508200103. www.pnas.orgcgidoi10.1073pnas.0508200103 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [62].Nagy PD, Carpenter CD, Simon AE. A novel 3’-end repair mechanism in an RNA virus. Proc Natl Acad Sci [Internet]. 1997 Feb 18;94(4):1113–8. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.94.4.1113 [DOI] [PMC free article] [PubMed]; Nagy PD, Carpenter CD, Simon AE. A novel 3’-end repair mechanism in an RNA virus. Proc Natl Acad Sci [Internet] 1997 Feb 18;94(4):1113–8. doi: 10.1073/pnas.94.4.1113. http://www.pnas.org/cgi/doi/10.1073/pnas.94.4.1113 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [63].Chen P, Jiang M, Hu T, Liu Q, Chen XS, Guo D. Biochemical characterization of exoribonuclease encoded by SARS coronavirus. J Biochem Mol Biol [Internet]. 2007 [cited 2021 Feb 11];40(5):649–55. Available from: https://pubmed.ncbi.nlm.nih.gov/17927896/ [DOI] [PubMed]; Chen P, Jiang M, Hu T, Liu Q, Chen XS, Guo D. Biochemical characterization of exoribonuclease encoded by SARS coronavirus. J Biochem Mol Biol [Internet] 2007 [cited 2021 Feb 11];40(5):649–55. doi: 10.5483/bmbrep.2007.40.5.649. https://pubmed.ncbi.nlm.nih.gov/17927896/ . Available from: [DOI] [PubMed] [Google Scholar]
- [64].Barr JN, Fearns R. How RNA viruses maintain their genome integrity. J Gen Virol [Internet]. 2010 Jun 1;91(6):1373–87. Available from: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.020818-0 [DOI] [PubMed]; Barr JN, Fearns R. How RNA viruses maintain their genome integrity. J Gen Virol [Internet] 2010 Jun 1;91(6):1373–87. doi: 10.1099/vir.0.020818-0. https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.020818-0 . Available from: [DOI] [PubMed] [Google Scholar]
- [65].Saunders RDC, Boubriak I, Clancy DJ, Cox LS. Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity. Aging Cell [Internet]. 2008 Jun;7(3):418–25. Available from: http://doi.wiley.com/10.1111/j.1474-9726.2008.00388.x [DOI] [PMC free article] [PubMed]; Saunders RDC, Boubriak I, Clancy DJ, Cox LS. Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity. Aging Cell [Internet] 2008 Jun;7(3):418–25. doi: 10.1111/j.1474-9726.2008.00388.x. http://doi.wiley.com/10.1111/j.1474-9726.2008.00388.x . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [66].Becares M, Pascual-Iglesias A, Nogales A, Sola I, Enjuanes L, Zuñiga S. Mutagenesis of coronavirus nsp14 reveals its potential role in modulation of the innate immune response. J Virol. 2016;90(11):5399–414. [DOI] [PMC free article] [PubMed]; Becares M, Pascual-Iglesias A, Nogales A, Sola I, Enjuanes L, Zuñiga S. Mutagenesis of coronavirus nsp14 reveals its potential role in modulation of the innate immune response. J Virol. 2016;90(11):5399–414. doi: 10.1128/JVI.03259-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [67].Eckerle LD, Lu X, Sperry SM, Choi L, Denison MR. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J Virol. 2007;81(22):12135–44. [DOI] [PMC free article] [PubMed]; Eckerle LD, Lu X, Sperry SM, Choi L, Denison MR. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J Virol. 2007;81(22):12135–44. doi: 10.1128/JVI.01296-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [68].Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A, et al. Remdesivir in treatment of COVID-19: a systematic benefit–risk assessment. Drug Saf [Internet]. 2020 Jul 28;43(7):645–56. Available from: http://link.springer.com/10.1007/s40264-020-00952-1 [DOI] [PMC free article] [PubMed]; Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A. et al. Remdesivir in treatment of COVID-19: a systematic benefit–risk assessment. Drug Saf [Internet] 2020 Jul 28;43(7):645–56. doi: 10.1007/s40264-020-00952-1. http://link.springer.com/10.1007/s40264-020-00952-1 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [69].Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Sevestre J, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study. Travel Med Infect Dis [Internet]. 2020 Mar;34:101663. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1477893920301319 [DOI] [PMC free article] [PubMed]; Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Sevestre J. et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study. Travel Med Infect Dis [Internet] 2020 Mar;34:101663. doi: 10.1016/j.tmaid.2020.101663. https://linkinghub.elsevier.com/retrieve/pii/S1477893920301319 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [70].Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet [Internet]. 2020 Aug 15 [cited 2021 Feb 11];396(10249):479–88. [DOI] [PMC free article] [PubMed]; Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH. et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet [Internet] 2020 Aug 15 [cited 2021 Feb 11];396(10249):479–88. doi: 10.1016/S0140-6736(20)31605-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [71].Haidere MF, Ratan ZA, Nowroz S, Zaman SB, Jung Y-J, Hosseinzadeh H, et al. COVID-19 vaccine: critical questions with complicated answers. Biomol Ther (Seoul). 2021 Jan;29(1):1–10. [DOI] [PMC free article] [PubMed]; Haidere MF, Ratan ZA, Nowroz S, Zaman SB, Jung Y-J, Hosseinzadeh H. et al. COVID-19 vaccine: critical questions with complicated answers. Biomol Ther (Seoul) 2021 Jan;29(1):1–10. doi: 10.4062/biomolther.2020.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [72].Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727–33. [DOI] [PMC free article] [PubMed]; Zhu N, Zhang D, Wang W, Li X, Yang B, Song J. et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727–33. doi: 10.1056/NEJMoa2001017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [73].Kuo TY, Lin MY, Coffman RL, Campbell JD, Traquina P, Lin YJ, et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci Rep. 2020 Dec 1;10:1. [DOI] [PMC free article] [PubMed]; Kuo TY, Lin MY, Coffman RL, Campbell JD, Traquina P, Lin YJ. et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci Rep. 2020 Dec 1;10:1. doi: 10.1038/s41598-020-77077-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [74].Wang F, Kream RM, Stefano GB. An evidence based perspective on mRNA-SARScov-2 vaccine development [Internet]. Med Sci Monit. 2020 [cited 2021 Feb 11];26:1–8. Available from: https://pubmed.ncbi.nlm.nih.gov/32366816/ [DOI] [PMC free article] [PubMed]; Wang F, Kream RM, Stefano GB. An evidence based perspective on mRNA-SARScov-2 vaccine development [Internet] Med Sci Monit. 2020 [cited 2021 Feb 11];26:1–8. doi: 10.12659/MSM.924700. https://pubmed.ncbi.nlm.nih.gov/32366816/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [75].Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M, et al. Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature [Internet]. 2021 Feb 1 [cited 2021 Feb 11];592:1–10. Available from: https://www.nature.com/articles/s41586-021-03275-y [DOI] [PubMed]; Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M. et al. Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature [Internet] 2021 Feb 1 [cited 2021 Feb 11];592:1–10. doi: 10.1038/s41586-021-03275-y. https://www.nature.com/articles/s41586-021-03275-y . Available from: [DOI] [PubMed] [Google Scholar]
- [76].Walsh EE, Frenck RW, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med [Internet]. 2020 Dec 17 [cited 2021 Feb 11];383(25):2439–50. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2027906 [DOI] [PMC free article] [PubMed]; Walsh EE, Frenck RW, Falsey AR, Kitchin N, Absalon J, Gurtman A. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med [Internet] 2020 Dec 17 [cited 2021 Feb 11];383(25):2439–50. doi: 10.1056/NEJMoa2027906. http://www.nejm.org/doi/10.1056/NEJMoa2027906 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [77].Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature [Internet]. 2020 Oct 22 [cited 2021 Feb 11];586(7830):567–71. Available from: https://doi.org/10.1038/s41586-020-2622-0 [DOI] [PMC free article] [PubMed]; Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature [Internet] 2020 Oct 22 [cited 2021 Feb 11];586(7830):567–71. doi: 10.1038/s41586-020-2622-0. . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [78].Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med [Internet]. 2020 Dec 17 [cited 2021 Feb 11];383(25):2427–38. Available from: https://pubmed.ncbi.nlm.nih.gov/32991794/ [DOI] [PMC free article] [PubMed]; Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M. et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med [Internet] 2020 Dec 17 [cited 2021 Feb 11];383(25):2427–38. doi: 10.1056/NEJMoa2028436. https://pubmed.ncbi.nlm.nih.gov/32991794/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [79].Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet [Internet]. 2020 Aug 15 [cited 2021 Feb 11];396(10249):467–78. [DOI] [PMC free article] [PubMed]; Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet [Internet] 2020 Aug 15 [cited 2021 Feb 11];396(10249):467–78. doi: 10.1016/S0140-6736(20)31604-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [80].van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature [Internet]. 2020 Oct 22 [cited 2021 Feb 11];586(7830):578–82. Available from: https://doi.org/10.1038/s41586-020-2608-y [DOI] [PMC free article] [PubMed]; van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR. et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature [Internet] 2020 Oct 22 [cited 2021 Feb 11];586(7830):578–82. doi: 10.1038/s41586-020-2608-y. . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [81].Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis [Internet]. 2021 Feb 1 [cited 2021 Mar 11];21(2):181–92. Available from: www.thelancet.com/infection [DOI] [PMC free article] [PubMed]; Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K. et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis [Internet] 2021 Feb 1 [cited 2021 Mar 11];21(2):181–92. doi: 10.1016/S1473-3099(20)30843-4. www.thelancet.com/infection . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [82].Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet [Internet]. 2020 Sep 26 [cited 2021 Feb 11];396(10255):887–97. [DOI] [PMC free article] [PubMed]; Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet [Internet] 2020 Sep 26 [cited 2021 Feb 11];396(10255):887–97. doi: 10.1016/S0140-6736(20)31866-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [83].Lundstrom K. Viral vectors for COVID-19 vaccine development. Viruses [Internet]. 2021 Feb 19 [cited 2021 Mar 11];13(2):317. Available from: https://www.mdpi.com/1999-4915/13/2/317 [DOI] [PMC free article] [PubMed]; Lundstrom K. Viral vectors for COVID-19 vaccine development. Viruses [Internet] 2021 Feb 19 [cited 2021 Mar 11];13(2):317. doi: 10.3390/v13020317. https://www.mdpi.com/1999-4915/13/2/317 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [84].Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines. Vaccine analysis: strategies, principles, and control [Internet]. Berlin Heidelberg: Springer; 2015 [cited 2021 Mar 11]. p. 45–80. Available from: https://link.springer.com/chapter/10.1007/978-3-662-45024-6_2; Sanders B, Koldijk M, Schuitemaker H. Vaccine analysis: strategies, principles, and control [Internet] Berlin Heidelberg: Springer; 2015 [cited 2021 Mar 11]. Inactivated viral vaccines; pp. p. 45–80.https://link.springer.com/chapter/10.1007/978-3-662-45024-6_2 . Available from: [Google Scholar]
- [85].Hicks DJ, Fooks AR, Johnson N. Developments in rabies vaccines [Internet]. Clin Exp Immunol. 2012 [cited 2021 Mar 11];169:199–204. Available from: https://pubmed.ncbi.nlm.nih.gov/22861358/ [DOI] [PMC free article] [PubMed]; Hicks DJ, Fooks AR, Johnson N. Developments in rabies vaccines [Internet] Clin Exp Immunol. 2012 [cited 2021 Mar 11];169:199–204. doi: 10.1111/j.1365-2249.2012.04592.x. https://pubmed.ncbi.nlm.nih.gov/22861358/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [86].Barrett PN, Mundt W, Kistner O, Howard MK. Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines [Internet]. Expert Rev Vaccines. 2009 [cited 2021 Mar 11];8:607–18. Available from: https://pubmed.ncbi.nlm.nih.gov/19397417/ [DOI] [PubMed]; Barrett PN, Mundt W, Kistner O, Howard MK. Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines [Internet] Expert Rev Vaccines. 2009 [cited 2021 Mar 11];8:607–18. doi: 10.1586/erv.09.19. https://pubmed.ncbi.nlm.nih.gov/19397417/ . Available from: [DOI] [PubMed] [Google Scholar]
- [87].Madhusudana SN, Shamsundar R, Seetharaman S. In vitro inactivation of the rabies virus by ascorbic acid. Int J Infect Dis [Internet]. 2004 [cited 2021 Mar 11];8(1):21–5. Available from: https://pubmed.ncbi.nlm.nih.gov/14690777/ [DOI] [PubMed]; Madhusudana SN, Shamsundar R, Seetharaman S. In vitro inactivation of the rabies virus by ascorbic acid. Int J Infect Dis [Internet] 2004 [cited 2021 Mar 11];8(1):21–5. doi: 10.1016/j.ijid.2003.09.002. https://pubmed.ncbi.nlm.nih.gov/14690777/ . Available from: [DOI] [PubMed] [Google Scholar]
- [88].Bahnemann HG. Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine [Internet]. Vaccine. 1990 [cited 2021 Mar 12];8:299–303. Available from: https://pubmed.ncbi.nlm.nih.gov/2204242/ [DOI] [PMC free article] [PubMed]; Bahnemann HG. Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine [Internet] Vaccine. 1990 [cited 2021 Mar 12];8:299–303. doi: 10.1016/0264-410X(90)90083-X. https://pubmed.ncbi.nlm.nih.gov/2204242/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [89].Amanna IJ, Raué HP, Slifka MK. Development of a new hydrogen peroxide-based vaccine platform. Nat Med [Internet]. 2012 Jun [cited 2021 Mar 11];18(6):974–9. Available from: https://pubmed.ncbi.nlm.nih.gov/22635006/ [DOI] [PMC free article] [PubMed]; Amanna IJ, Raué HP, Slifka MK. Development of a new hydrogen peroxide-based vaccine platform. Nat Med [Internet] 2012 Jun [cited 2021 Mar 11];18(6):974–9. doi: 10.1038/nm.2763. https://pubmed.ncbi.nlm.nih.gov/22635006/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [90].Metz B, Kersten GFA, Hoogerhout P, Brugghe HF, Timmermans HAM, De Jong A, et al. Identification of formaldehyde-induced modifications in proteins: reactions with model peptides. J Biol Chem [Internet]. 2004 Feb 20 [cited 2021 Mar 12];279(8):6235–43. Available from: https://pubmed.ncbi.nlm.nih.gov/14638685/ [DOI] [PubMed]; Metz B, Kersten GFA, Hoogerhout P, Brugghe HF, Timmermans HAM, De Jong A. et al. Identification of formaldehyde-induced modifications in proteins: reactions with model peptides. J Biol Chem [Internet] 2004 Feb 20 [cited 2021 Mar 12];279(8):6235–43. doi: 10.1074/jbc.M310752200. https://pubmed.ncbi.nlm.nih.gov/14638685/ . Available from: [DOI] [PubMed] [Google Scholar]
- [91].Lawrence SA. beta-Propiolactone: viral inactivation in vaccines and plasma products. PDA J Pharm Sci Technol. 2000;54(3):209–17. [PubMed]; Lawrence SA. beta-Propiolactone: viral inactivation in vaccines and plasma products. PDA J Pharm Sci Technol. 2000;54(3):209–17. [PubMed] [Google Scholar]
- [92].Campbell CH, Barber TL, Knudsen RC, Swaney LM. Immune response of mice and sheep to bluetongue virus inactivated by gamma irradiation. Prog Clin Biol Res [Internet]. 1985 Jan 1 [cited 2021 Mar 12];178:639–47. Available from: https://europepmc.org/article/med/2989913 [PubMed]; Campbell CH, Barber TL, Knudsen RC, Swaney LM. Immune response of mice and sheep to bluetongue virus inactivated by gamma irradiation. Prog Clin Biol Res [Internet] 1985 Jan 1 [cited 2021 Mar 12];178:639–47. https://europepmc.org/article/med/2989913 . Available from: [PubMed] [Google Scholar]
- [93].Reitman M, Tribble HR, Green L. Gamma-irradiated Venezuelan equine encephalitis vaccines. Appl Microbiol [Internet]. 1970 [cited 2021 Mar 11];19(5):763–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC376784/?report=abstract [DOI] [PMC free article] [PubMed]; Reitman M, Tribble HR, Green L. Gamma-irradiated Venezuelan equine encephalitis vaccines. Appl Microbiol [Internet] 1970 [cited 2021 Mar 11];19(5):763–7. doi: 10.1128/am.19.5.763-767.1970. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC376784/?report=abstract . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [94].Wiktor TJ, Aaslestad HG, Kaplan MM. Immunogenicity of rabies virus inactivated by -propiolactone, acetylethyleneimine, and ionizing irradiation. Appl Microbiol [Internet]. 1972 [cited 2021 Mar 11];23(5):914–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC380470/?report=abstract [DOI] [PMC free article] [PubMed]; Wiktor TJ, Aaslestad HG, Kaplan MM. Immunogenicity of rabies virus inactivated by -propiolactone, acetylethyleneimine, and ionizing irradiation. Appl Microbiol [Internet] 1972 [cited 2021 Mar 11];23(5):914–8. doi: 10.1128/am.23.5.914-918.1972. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC380470/?report=abstract . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [95].Marennikova SS, Macevic GR. Experimental study of the role of inactivated vaccine in two step vaccination against smallpox bull world health organ [Internet]. 1975 Jan 1 [cited 2021 Mar 11];52(1):51–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/1082382/?tool=EBI [PMC free article] [PubMed]; Marennikova SS, Macevic GR. Experimental study of the role of inactivated vaccine in two step vaccination against smallpox bull world health organ [Internet] 1975 Jan 1 [cited 2021 Mar 11];52(1):51–6. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/1082382/?tool=EBI . Available from: [PMC free article] [PubMed] [Google Scholar]
- [96].Mullbacher A, Ada GL, Tha Hla R. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses. Immunol Cell Biol [Internet]. 1988 [cited 2021 Mar 11];66(2):153–7. Available from: https://pubmed.ncbi.nlm.nih.gov/2846435/ [DOI] [PubMed]; Mullbacher A, Ada GL, Tha Hla R. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses. Immunol Cell Biol [Internet] 1988 [cited 2021 Mar 11];66(2):153–7. doi: 10.1038/icb.1988.19. https://pubmed.ncbi.nlm.nih.gov/2846435/ . Available from: [DOI] [PubMed] [Google Scholar]
- [97].Kang CY, Gao Y. Killed whole-HIV vaccine, employing a well established strategy for antiviral vaccines [Internet]. AIDS Res Ther. 2017 [cited 2021 Feb 11];14:47. Available from: https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0176-5 [DOI] [PMC free article] [PubMed]; Kang CY, Gao Y. Killed whole-HIV vaccine, employing a well established strategy for antiviral vaccines [Internet] AIDS Res Ther. 2017 [cited 2021 Feb 11];14:47. doi: 10.1186/s12981-017-0176-5. https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0176-5 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [98].Marzi A, Halfmann P, Hill-Batorski L, Feldmann F, Shupert WL, Neumann G, et al. An Ebola whole-virus vaccine is protective in nonhuman primates. Science (80) [Internet]. 2015 Apr 24 [cited 2021 Feb 11];348(6233):439–42. Available from: https://pubmed.ncbi.nlm.nih.gov/25814063/ [DOI] [PMC free article] [PubMed]; Marzi A, Halfmann P, Hill-Batorski L, Feldmann F, Shupert WL, Neumann G. et al. An Ebola whole-virus vaccine is protective in nonhuman primates. Science (80) [Internet] 2015 Apr 24 [cited 2021 Feb 11];348(6233):439–42. doi: 10.1126/science.aaa4919. https://pubmed.ncbi.nlm.nih.gov/25814063/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [99].Shahrudin S, Chen C, David SC, Singleton EV, Davies J, Kirkwood CD, et al. Gamma-irradiated rotavirus: a possible whole virus inactivated vaccine. PLoS One [Internet]. 2018 Jun 7 [cited 2021 Feb 11];13(6):e0198182. Available from: https://dx.plos.org/10.1371/journal.pone.0198182 [DOI] [PMC free article] [PubMed]; Shahrudin S, Chen C, David SC, Singleton EV, Davies J, Kirkwood CD. et al. Gamma-irradiated rotavirus: a possible whole virus inactivated vaccine. PLoS One [Internet] 2018 Jun 7 [cited 2021 Feb 11];13(6):e0198182. doi: 10.1371/journal.pone.0198182. https://dx.plos.org/10.1371/journal.pone.0198182 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [100].Tobin GJ, Tobin JK, Gaidamakova EK, Wiggins TJ, Bushnell RV, Lee W-M, et al. A novel gamma radiation-inactivated sabin-based polio vaccine. In: Alsharifi M, editor. PLoS One [Internet]. 2020 Jan 30 [cited 2021 Feb 11];15(1):e0228006. Available from: https://dx.plos.org/10.1371/journal.pone.0228006 [DOI] [PMC free article] [PubMed]; Tobin GJ, Tobin JK, Gaidamakova EK, Wiggins TJ, Bushnell RV, Lee W-M. et al. A novel gamma radiation-inactivated sabin-based polio vaccine. In: Alsharifi M, editor. PLoS One [Internet] 2020 Jan 30 [cited 2021 Feb 11];15(1):e0228006. doi: 10.1371/journal.pone.0228006. https://dx.plos.org/10.1371/journal.pone.0228006 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [101].Feldmann F, Shupert WL, Haddock E, Twardoski B, Feldmann H. Gamma irradiation as an effective method for inactivation of emerging viral pathogens. Am J Trop Med Hyg [Internet]. 2019 [cited 2021 Feb 11];100(5):1275–7. Available from: https://pubmed.ncbi.nlm.nih.gov/30860018/ [DOI] [PMC free article] [PubMed]; Feldmann F, Shupert WL, Haddock E, Twardoski B, Feldmann H. Gamma irradiation as an effective method for inactivation of emerging viral pathogens. Am J Trop Med Hyg [Internet] 2019 [cited 2021 Feb 11];100(5):1275–7. doi: 10.4269/ajtmh.18-0937. https://pubmed.ncbi.nlm.nih.gov/30860018/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [102].Jahrling PB, Stephenson EH. Protective efficacies of live attenuated and formaldehyde-inactivated Venezuelan equine encephalitis virus vaccines against aerosol challenge in hamsters. J Clin Microbiol [Internet]. 1984 [cited 2021 Mar 12];19(3):429–31. Available from: https://pubmed.ncbi.nlm.nih.gov/pmc/articles/PMC271080/?report=abstract [DOI] [PMC free article] [PubMed]; Jahrling PB, Stephenson EH. Protective efficacies of live attenuated and formaldehyde-inactivated Venezuelan equine encephalitis virus vaccines against aerosol challenge in hamsters. J Clin Microbiol [Internet] 1984 [cited 2021 Mar 12];19(3):429–31. doi: 10.1128/jcm.19.3.429-431.1984. https://pubmed.ncbi.nlm.nih.gov/pmc/articles/PMC271080/?report=abstract . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [103].Delrue I, Verzele D, Madder A, Nauwynck HJ. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges. Expert Rev Vaccines [Internet]. 2012 Jun 9 [cited 2021 Mar 12];11(6):695–719. Available from: http://www.tandfonline.com/doi/full/10.1586/erv.12.38 [DOI] [PubMed]; Delrue I, Verzele D, Madder A, Nauwynck HJ. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges. Expert Rev Vaccines [Internet] 2012 Jun 9 [cited 2021 Mar 12];11(6):695–719. doi: 10.1586/erv.12.38. http://www.tandfonline.com/doi/full/10.1586/erv.12.38 . Available from: [DOI] [PubMed] [Google Scholar]
- [104].Ohshima H, Iida Y, Matsuda A, Kuwabara M. Damage induced by hydroxyl radicals generated in the hydration layer of GAMMA-irradiated frozen aqueous solution of DNA. J Radiat Res [Internet]. 1996 Sep 1 [cited 2021 Mar 12];37(3):199–207. Available from: https://academic.oup.com/jrr/article-lookup/doi/10.1269/jrr.37.199 [DOI] [PubMed]; Ohshima H, Iida Y, Matsuda A, Kuwabara M. Damage induced by hydroxyl radicals generated in the hydration layer of GAMMA-irradiated frozen aqueous solution of DNA. J Radiat Res [Internet] 1996 Sep 1 [cited 2021 Mar 12];37(3):199–207. doi: 10.1269/jrr.37.199. https://academic.oup.com/jrr/article-lookup/doi/10.1269/jrr.37.199 . Available from: [DOI] [PubMed] [Google Scholar]
- [105].Alsharifi M, Müllbacher A. The γ-irradiated influenza vaccine and the prospect of producing safe vaccines in general. Immunol Cell Biol. 2010;88:103–4. [DOI] [PubMed]; Alsharifi M, Müllbacher A. The γ-irradiated influenza vaccine and the prospect of producing safe vaccines in general. Immunol Cell Biol. 2010;88:103–4. doi: 10.1038/icb.2009.81. [DOI] [PubMed] [Google Scholar]
- [106].Mullbacher A, Marshall ID, Ferris P. Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays. J Gen Virol [Internet]. 1986 [cited 2021 Mar 12];67(2):295–9. Available from: https://pubmed.ncbi.nlm.nih.gov/3003237/ [DOI] [PubMed]; Mullbacher A, Marshall ID, Ferris P. Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays. J Gen Virol [Internet] 1986 [cited 2021 Mar 12];67(2):295–9. doi: 10.1099/0022-1317-67-2-295. https://pubmed.ncbi.nlm.nih.gov/3003237/ . Available from: [DOI] [PubMed] [Google Scholar]
- [107].Lowy RJ, Vavrina GA, LaBarre DD. Comparison of gamma and neutron radiation inactivation of influenza A virus. Antiviral Res [Internet]. 2001 [cited 2021 Feb 11];52(3):261–73. Available from: https://pubmed.ncbi.nlm.nih.gov/11675143/ [DOI] [PubMed]; Lowy RJ, Vavrina GA, LaBarre DD. Comparison of gamma and neutron radiation inactivation of influenza A virus. Antiviral Res [Internet] 2001 [cited 2021 Feb 11];52(3):261–73. doi: 10.1016/s0166-3542(01)00169-3. https://pubmed.ncbi.nlm.nih.gov/11675143/ . Available from: [DOI] [PubMed] [Google Scholar]
- [108].Patterson EI, Prince T, Anderson ER, Casas-Sanchez A, Smith SL, Cansado-Utrilla C, et al. Methods of inactivation of SARS-CoV-2 for downstream biological assays. J Infect Dis [Internet]. 2020 Oct 1 [cited 2021 Feb 11];222(9):1462–7. Available from: https://academic.oup.com/jid/article/222/9/1462/5892951 [DOI] [PMC free article] [PubMed]; Patterson EI, Prince T, Anderson ER, Casas-Sanchez A, Smith SL, Cansado-Utrilla C. et al. Methods of inactivation of SARS-CoV-2 for downstream biological assays. J Infect Dis [Internet] 2020 Oct 1 [cited 2021 Feb 11];222(9):1462–7. doi: 10.1093/infdis/jiaa507. https://academic.oup.com/jid/article/222/9/1462/5892951 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [109].Koopmans M, Duizer E. Foodborne viruses: an emerging problem. Int J Food Microbiol. 2004 Jan;90(1):23–41. [DOI] [PMC free article] [PubMed]; Koopmans M, Duizer E. Foodborne viruses: an emerging problem. Int J Food Microbiol. 2004 Jan;90(1):23–41. doi: 10.1016/S0168-1605(03)00169-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [110].Duan S-M, Zhao X-S, Wen R-F, Huang J-J, Pi G-H, Zhang S-X, et al. Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. Biomed Environ Sci. 2003 Sep;16(3):246–55. [PubMed]; Duan S-M, Zhao X-S, Wen R-F, Huang J-J, Pi G-H, Zhang S-X. et al. Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. Biomed Environ Sci. 2003 Sep;16(3):246–55. [PubMed] [Google Scholar]
- [111].Darnell MER, Subbarao K, Feinstone SM, Taylor DR. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods [Internet]. 2004 Oct;121(1):85–91. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016609340400179X [DOI] [PMC free article] [PubMed]; Darnell MER, Subbarao K, Feinstone SM, Taylor DR. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods [Internet] 2004 Oct;121(1):85–91. doi: 10.1016/j.jviromet.2004.06.006. https://linkinghub.elsevier.com/retrieve/pii/S016609340400179X . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [112].Gerlach M, Wolff S, Ludwig S, Schäfer W, Keiner B, Roth NJ, et al. Rapid SARS-CoV-2 inactivation by commonly available chemicals on inanimate surfaces [Internet]. J Hosp Infect. 2020 [cited 2021 Feb 11];106:633–4. Available from: https://doi.org/10.1016/j.jhin.2020.09.001 [DOI] [PMC free article] [PubMed]; Gerlach M, Wolff S, Ludwig S, Schäfer W, Keiner B, Roth NJ. et al. Rapid SARS-CoV-2 inactivation by commonly available chemicals on inanimate surfaces [Internet] J Hosp Infect. 2020 [cited 2021 Feb 11];106:633–4. doi: 10.1016/j.jhin.2020.09.001. . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [113].Kumar A, Becker D, Adhikary A, Sevilla MD. Molecular sciences reaction of electrons with DNA: radiation damage to radiosensitization. mdpi.com [Internet]; 2019 [cited 2020 Aug 9]. Available from: www.mdpi.com/journal/ijms [DOI] [PMC free article] [PubMed]; Kumar A, Becker D, Adhikary A, Sevilla MD. mdpi.com [Internet] 2019 [cited 2020 Aug 9]. Molecular sciences reaction of electrons with DNA: radiation damage to radiosensitization.www.mdpi.com/journal/ijms . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [114].Alizadeh E, Orlando TM, Sanche L. Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA. Annu Rev Phys Chem [Internet]. 2015 Apr;66(1):379–98. Available from: http://www.annualreviews.org/doi/10.1146/annurev-physchem-040513-103605 [DOI] [PubMed]; Alizadeh E, Orlando TM, Sanche L. Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA. Annu Rev Phys Chem [Internet] 2015 Apr;66(1):379–98. doi: 10.1146/annurev-physchem-040513-103605. http://www.annualreviews.org/doi/10.1146/annurev-physchem-040513-103605 . Available from: [DOI] [PubMed] [Google Scholar]
- [115].O’Neill P, Stevens DL, Garman E. Physical and chemical considerations of damage induced in protein crystals by synchrotron radiation: a radiation chemical perspective. J Synchrotron Radiat. 2002;9(6):329–32. [DOI] [PubMed]; O’Neill P, Stevens DL, Garman E. Physical and chemical considerations of damage induced in protein crystals by synchrotron radiation: a radiation chemical perspective. J Synchrotron Radiat. 2002;9(6):329–32. doi: 10.1107/s0909049502014553. [DOI] [PubMed] [Google Scholar]
- [116].Bartels DM, Cook AR, Mudaliar M, Jonah CD. Spur decay of the solvated electron in picosecond radiolysis measured with time-correlated absorption spectroscopy. J Phys Chem A [Internet]. 2000 Mar;104(8):1686–91. Available from: https://pubs.acs.org/doi/10.1021/jp992723e; Bartels DM, Cook AR, Mudaliar M, Jonah CD. Spur decay of the solvated electron in picosecond radiolysis measured with time-correlated absorption spectroscopy. J Phys Chem A [Internet] 2000 Mar;104(8):1686–91. https://pubs.acs.org/doi/10.1021/jp992723e . Available from: [Google Scholar]
- [117].Uehara S, Nikjoo H. Monte Carlo simulation of water radiolysis for low-energy charged particles [Internet]. J Radiat Res. 2006 [cited 2020 Aug 9];47:69–81. Available from: http://jrr.jstage.jst.go.jp [DOI] [PubMed]; Uehara S, Nikjoo H. Monte Carlo simulation of water radiolysis for low-energy charged particles [Internet] J Radiat Res. 2006 [cited 2020 Aug 9];47:69–81. doi: 10.1269/jrr.47.69. http://jrr.jstage.jst.go.jp . Available from: [DOI] [PubMed] [Google Scholar]
- [118].Lytle CD, Sagripanti J-L. Predicted inactivation of viruses of relevance to biodefense by solar radiation. J Virol. 2005;79(22):14244–52. [DOI] [PMC free article] [PubMed]; Lytle CD, Sagripanti J-L. Predicted inactivation of viruses of relevance to biodefense by solar radiation. J Virol. 2005;79(22):14244–52. doi: 10.1128/JVI.79.22.14244-14252.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [119].Lomax ME, Folkes LK, O’neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol. 2013;25(10):578–85. [DOI] [PubMed]; Lomax ME, Folkes LK, O’neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol. 2013;25(10):578–85. doi: 10.1016/j.clon.2013.06.007. [DOI] [PubMed] [Google Scholar]
- [120].Gates KS. An overview of chemical processes that damage cellular DNA: spontaneous hydrolysis, alkylation, and reactions with radicals. Chem Res Toxicol. 2009;22(11):1747–60. [DOI] [PMC free article] [PubMed]; Gates KS. An overview of chemical processes that damage cellular DNA: spontaneous hydrolysis, alkylation, and reactions with radicals. Chem Res Toxicol. 2009;22(11):1747–60. doi: 10.1021/tx900242k. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [121].Sobotta L, Skupin-Mrugalska P, Mielcarek J, Goslinski T, Balzarini J. Photosensitizers mediated photodynamic inactivation against virus particles mini-reviews. Med Chem [Internet]. 2015 Apr 18 [cited 2021 Feb 11];15(6):503–21. Available from: https://pubmed.ncbi.nlm.nih.gov/25877599/ [DOI] [PubMed]; Sobotta L, Skupin-Mrugalska P, Mielcarek J, Goslinski T, Balzarini J. Photosensitizers mediated photodynamic inactivation against virus particles mini-reviews. Med Chem [Internet] 2015 Apr 18 [cited 2021 Feb 11];15(6):503–21. doi: 10.2174/1389557515666150415151505. https://pubmed.ncbi.nlm.nih.gov/25877599/ . Available from: [DOI] [PubMed] [Google Scholar]
- [122].Costa L, Faustino MAF, Neves MGPMS, Cunha Â, Almeida A. Photodynamic inactivation of mammalian viruses and bacteriophages [Internet]. Viruses. 2012 [cited 2021 Feb 11];4:1034–74. Available from: https://pubmed.ncbi.nlm.nih.gov/pmc/articles/PMC3407894/ [DOI] [PMC free article] [PubMed]; Costa L, Faustino MAF, Neves MGPMS, Cunha Â, Almeida A. Photodynamic inactivation of mammalian viruses and bacteriophages [Internet] Viruses. 2012 [cited 2021 Feb 11];4:1034–74. doi: 10.3390/v4071034. https://pubmed.ncbi.nlm.nih.gov/pmc/articles/PMC3407894/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [123].Lampe N, Karamitros M, Breton V, Brown JMC, Sakata D, Sarramia D, et al. Mechanistic DNA damage simulations in Geant4-DNA Part 2: electron and proton damage in a bacterial cell. Phys Med. 2018;48:146–55. [DOI] [PubMed]; Lampe N, Karamitros M, Breton V, Brown JMC, Sakata D, Sarramia D. et al. Mechanistic DNA damage simulations in Geant4-DNA Part 2: electron and proton damage in a bacterial cell. Phys Med. 2018;48:146–55. doi: 10.1016/j.ejmp.2017.12.008. [DOI] [PubMed] [Google Scholar]
- [124].Sommer R, Pribil W, Appelt S, Gehringer P, Eschweiler H, Leth H, et al. Inactivation of bacteriophages in water by means of non-ionizing (UV-253.7 nm) and ionizing (gamma) radiation: a comparative approach. Water Res. 2001;35(13):3109–16. [DOI] [PubMed]; Sommer R, Pribil W, Appelt S, Gehringer P, Eschweiler H, Leth H. et al. Inactivation of bacteriophages in water by means of non-ionizing (UV-253.7 nm) and ionizing (gamma) radiation: a comparative approach. Water Res. 2001;35(13):3109–16. doi: 10.1016/s0043-1354(01)00030-6. [DOI] [PubMed] [Google Scholar]
- [125].de Roda Husman AM, Bijkerk P, Lodder W, van den Berg H, Pribil W, Cabaj A, et al. Calicivirus Inactivation by nonionizing (253.7-nanometer-wavelength [UV]) and ionizing (gamma) radiation. Appl Environ Microbiol [Internet]. 2004 Sep;70(9):5089–93. Available from: https://aem.asm.org/content/70/9/5089 [DOI] [PMC free article] [PubMed]; de Roda Husman AM, Bijkerk P, Lodder W, van den Berg H, Pribil W, Cabaj A. et al. Calicivirus Inactivation by nonionizing (253.7-nanometer-wavelength [UV]) and ionizing (gamma) radiation. Appl Environ Microbiol [Internet] 2004 Sep;70(9):5089–93. doi: 10.1128/AEM.70.9.5089-5093.2004. https://aem.asm.org/content/70/9/5089 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [126].Wang T-Y, Libardo MDJ, Angeles-Boza AM, Pellois J-P. Membrane oxidation in cell delivery and cell killing applications. ACS Chem Biol [Internet]. 2017 May 19;12(5):1170–82. Available from: https://pubs.acs.org/doi/10.1021/acschembio.7b00237 [DOI] [PMC free article] [PubMed]; Wang T-Y, Libardo MDJ, Angeles-Boza AM, Pellois J-P. Membrane oxidation in cell delivery and cell killing applications. ACS Chem Biol [Internet] 2017 May 19;12(5):1170–82. doi: 10.1021/acschembio.7b00237. https://pubs.acs.org/doi/10.1021/acschembio.7b00237 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [127].Hume AJ, Ames J, Rennick LJ, Duprex WP, Marzi A, Tonkiss J, et al. Inactivation of RNA viruses by gamma irradiation: a study on mitigating factors. Viruses. 2016;8(7):204. [DOI] [PMC free article] [PubMed]; Hume AJ, Ames J, Rennick LJ, Duprex WP, Marzi A, Tonkiss J. et al. Inactivation of RNA viruses by gamma irradiation: a study on mitigating factors. Viruses. 2016;8(7):204. doi: 10.3390/v8070204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [128].Nims RW, Gauvin G, Plavsic M. Gamma irradiation of animal sera for inactivation of viruses and mollicutes–a review. Biologicals. 2011;39(6):370–7. [DOI] [PubMed]; Nims RW, Gauvin G, Plavsic M. Gamma irradiation of animal sera for inactivation of viruses and mollicutes–a review. Biologicals. 2011;39(6):370–7. doi: 10.1016/j.biologicals.2011.05.003. [DOI] [PubMed] [Google Scholar]
- [129].Durante M, Schulze K, Incerti S, Francis Z, Zein S, Guzmán CA. Virus irradiation and COVID-19 disease. Front Phys [Internet]. 2020 Oct 20 [cited 2021 Feb 11];8:565861. Available from: https://www.frontiersin.org/articles/10.3389/fphy.2020.565861/full; Durante M, Schulze K, Incerti S, Francis Z, Zein S, Guzmán CA. Virus irradiation and COVID-19 disease. Front Phys [Internet] 2020 Oct 20 [cited 2021 Feb 11];8:565861. https://www.frontiersin.org/articles/10.3389/fphy.2020.565861/full . Available from: [Google Scholar]
- [130].Zhao L, Mi D, Hu B, Sun Y. A generalized target theory and its applications. Sci Rep [Internet]. 2015 Nov 28;5(1):14568. Available from: http://www.nature.com/articles/srep14568 [DOI] [PMC free article] [PubMed]; Zhao L, Mi D, Hu B, Sun Y. A generalized target theory and its applications. Sci Rep [Internet] 2015 Nov 28;5(1):14568. doi: 10.1038/srep14568. http://www.nature.com/articles/srep14568 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [131].Nomiya T. Discussions on target theory: past and present. J Radiat Res [Internet]. 2013 Nov;54(6):1161–3. Available from: https://academic.oup.com/jrr/article-lookup/doi/10.1093/jrr/rrt075 [DOI] [PMC free article] [PubMed]; Nomiya T. Discussions on target theory: past and present. J Radiat Res [Internet] 2013 Nov;54(6):1161–3. doi: 10.1093/jrr/rrt075. https://academic.oup.com/jrr/article-lookup/doi/10.1093/jrr/rrt075 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [132].Pruß A, Schmidt T, Hoburg AT, Gohs U, Schumann W, Sim-Brandenburg J-W, et al. Original article originalarbeit inactivation effect of standard and fractionated electron beam irradiation on enveloped and non-enveloped viruses in a tendon transplant model. Transfus Med Hemother [Internet]. 2012 Feb [cited 2020 Aug 12];39(1):29–35. Available from: www.karger.com/tmh [DOI] [PMC free article] [PubMed]; Pruß A, Schmidt T, Hoburg AT, Gohs U, Schumann W, Sim-Brandenburg J-W. et al. Original article originalarbeit inactivation effect of standard and fractionated electron beam irradiation on enveloped and non-enveloped viruses in a tendon transplant model. Transfus Med Hemother [Internet] 2012 Feb [cited 2020 Aug 12];39(1):29–35. doi: 10.1159/000336380. www.karger.com/tmh . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [133].Feldmann F, Shupert WL, Haddock E, Twardoski B, Feldmann H. Gamma irradiation as an effective method for inactivation of emerging viral pathogens. Am J Trop Med Hyg [Internet]. 2019 May 1;100(5):1275–7. Available from: http://www.ajtmh.org/content/journals/10.4269/ajtmh.18-0937 [DOI] [PMC free article] [PubMed]; Feldmann F, Shupert WL, Haddock E, Twardoski B, Feldmann H. Gamma irradiation as an effective method for inactivation of emerging viral pathogens. Am J Trop Med Hyg [Internet] 2019 May 1;100(5):1275–7. doi: 10.4269/ajtmh.18-0937. http://www.ajtmh.org/content/journals/10.4269/ajtmh.18-0937 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [134].Leung A, Tran K, Audet J, Lavineway S, Bastien N, Krishnan J. In vitro Inactivation of SARS-CoV-2 using gamma radiation. Appl Biosaf [Internet]. 2020 Sep 1 [cited 2021 Feb 11];25(3):157–60. Available from: https://www.liebertpub.com/doi/10.1177/1535676020934242 [DOI] [PMC free article] [PubMed]; Leung A, Tran K, Audet J, Lavineway S, Bastien N, Krishnan J. In vitro Inactivation of SARS-CoV-2 using gamma radiation. Appl Biosaf [Internet] 2020 Sep 1 [cited 2021 Feb 11];25(3):157–60. doi: 10.1177/1535676020934242. https://www.liebertpub.com/doi/10.1177/1535676020934242 . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [135].Gauvin G. RN-P Journal of Pharmaceutical Science. Gamma-irradiation of serum for the inactivation of adventitious contaminants. journal.pda.org [Internet]; 2010 Undefined [cited 2020 Aug 9]. Available from: https://journal.pda.org/content/64/5/432.short [PubMed]; Gauvin G. RN-P Journal of Pharmaceutical Science. journal.pda.org [Internet] 2010 Undefined [cited 2020 Aug 9]. Gamma-irradiation of serum for the inactivation of adventitious contaminants.https://journal.pda.org/content/64/5/432.short . Available from: [PubMed] [Google Scholar]
- [136].Davison AJ. Herpesvirus systematics. Vet Microbiol. 2010 Jun;143(1):52–69. [DOI] [PMC free article] [PubMed]; Davison AJ. Herpesvirus systematics. Vet Microbiol. 2010 Jun;143(1):52–69. doi: 10.1016/j.vetmic.2010.02.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [137].Plavsic MZ, Daley JP, Danner DJ, Weppner DJ. Gamma irradiation of bovine sera. Dev Biol Stand. 1999;99:95–109. [PubMed]; Plavsic MZ, Daley JP, Danner DJ, Weppner DJ. Gamma irradiation of bovine sera. Dev Biol Stand. 1999;99:95–109. [PubMed] [Google Scholar]
- [138].Moss B. Poxvirus DNA replication. cshperspectives.cshlp.org [Internet]. Vol. 5, 2013 Sep [cited 2020 Aug 14]. p. 9. Available from: http://cshperspectives.cshlp.org/; Moss B. Poxvirus DNA replication. cshperspectives.cshlp.org [Internet] 2013 Sep [cited 2020 Aug 14];Vol. 5:p. 9. http://cshperspectives.cshlp.org/ . Available from: [Google Scholar]
- [139].Thomas FC, Davies AG, Dulac GC, Willis NG, Papp-Vid G, Girard A. Gamma ray inactivation of some animal viruses. Can J Comp Med [Internet]. 1981 [cited 2021 Feb 11];45(4):397–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1320171/?report=abstract [PMC free article] [PubMed]; Thomas FC, Davies AG, Dulac GC, Willis NG, Papp-Vid G, Girard A. Gamma ray inactivation of some animal viruses. Can J Comp Med [Internet] 1981 [cited 2021 Feb 11];45(4):397–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1320171/?report=abstract . Available from: [PMC free article] [PubMed] [Google Scholar]
- [140].Cox RM, Plemper RK. Structure and organization of paramyxovirus particles. Curr Opin Virol. 2017;24:105–14. [DOI] [PMC free article] [PubMed]; Cox RM, Plemper RK. Structure and organization of paramyxovirus particles. Curr Opin Virol. 2017;24:105–14. doi: 10.1016/j.coviro.2017.05.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [141].Neufeldt CJ, Cortese M, Acosta EG, Bartenschlager R. Rewiring cellular networks by members of the Flaviviridae family. naturecom [Internet]. 2018 Feb 12 [cited 2020 Aug 14];16(3):125–42. Available from: www.nature.com/nrmicro [DOI] [PMC free article] [PubMed]; Neufeldt CJ, Cortese M, Acosta EG, Bartenschlager R. Rewiring cellular networks by members of the Flaviviridae family. naturecom [Internet] 2018 Feb 12 [cited 2020 Aug 14];16(3):125–42. doi: 10.1038/nrmicro.2017.170. www.nature.com/nrmicro . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [142].House C, House JA, Yedloutschnig RJ. Inactivation of viral agents in bovine serum by gamma irradiation1. Can J Microbiol. 1990;36:737–40. [DOI] [PubMed]; House C, House JA, Yedloutschnig RJ. Inactivation of viral agents in bovine serum by gamma irradiation1. Can J Microbiol. 1990;36:737–40. doi: 10.1139/m90-126. [DOI] [PubMed] [Google Scholar]
- [143].Phan MVT, Ngo Tri T, Hong Anh P, Baker S, Kellam P, Cotten M. Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains. Virus Evol [Internet]. 2018 Jul 1 [cited 2020 Aug 14];4(2):1–12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295324/?report=abstract [DOI] [PMC free article] [PubMed]; Phan MVT, Ngo Tri T, Hong Anh P, Baker S, Kellam P, Cotten M. Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains. Virus Evol [Internet] 2018 Jul 1 [cited 2020 Aug 14];4(2):1–12. doi: 10.1093/ve/vey035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295324/?report=abstract . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [144].Dietzgen RG, Kondo H, Goodin MM, Kurath G, Vasilakis N. The family Rhabdoviridae: mono- and bipartite negative-sense RNA viruses with diverse genome organization and common evolutionary origins [Internet]. Virus Res. 2017 [cited 2021 Feb 11];227:158–70. Available from: https://pubmed.ncbi.nlm.nih.gov/27773769/ [DOI] [PMC free article] [PubMed]; Dietzgen RG, Kondo H, Goodin MM, Kurath G, Vasilakis N. The family Rhabdoviridae: mono- and bipartite negative-sense RNA viruses with diverse genome organization and common evolutionary origins [Internet] Virus Res. 2017 [cited 2021 Feb 11];227:158–70. doi: 10.1016/j.virusres.2016.10.010. https://pubmed.ncbi.nlm.nih.gov/27773769/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [145].Klemm C, Reguera J, Cusack S, Zielecki F, Kochs G, Weber F. Systems to establish bunyavirus genome replication in the absence of transcription. J Virol [Internet]. 2013 Jul 15 [cited 2021 Feb 11];87(14):8205–12. Available from: http://jvi.asm.org/ [DOI] [PMC free article] [PubMed]; Klemm C, Reguera J, Cusack S, Zielecki F, Kochs G, Weber F. Systems to establish bunyavirus genome replication in the absence of transcription. J Virol [Internet] 2013 Jul 15 [cited 2021 Feb 11];87(14):8205–12. doi: 10.1128/JVI.00371-13. http://jvi.asm.org/ . Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- [146].Akashi H, Onuma S, Nagano H, Ohta M, Fukutomi T. Detection and differentiation of Aino and Akabane Simbu serogroup bunyaviruses by nested polymerase chain reaction. Arch Virol [Internet]. 1999 [cited 2021 Feb 11];144(11):2101–9. Available from: https://pubmed.ncbi.nlm.nih.gov/10603165/ [DOI] [PubMed]; Akashi H, Onuma S, Nagano H, Ohta M, Fukutomi T. Detection and differentiation of Aino and Akabane Simbu serogroup bunyaviruses by nested polymerase chain reaction. Arch Virol [Internet] 1999 [cited 2021 Feb 11];144(11):2101–9. doi: 10.1007/s007050050625. https://pubmed.ncbi.nlm.nih.gov/10603165/ . Available from: [DOI] [PubMed] [Google Scholar]