| Remdesivir |
Inhibiting the RNA-dependent RNA polymerase |
• It was originally developed by Gilead Sciences (USA) against the Ebola virus as a prodrug because its structure resembles endogenous adenosine8
|
| • It has been previously shown to display antiviral activities against coronaviruses, especially SARS-CoV9
|
| • Remdesivir is now being tested in different countries, two randomized phases, III trials10,11
|
| Favipiravir |
• It was developed by Toyama Chemical (Japan) for the treatment of influenza |
| • It's a prodrug structurally resembling the endogenous guanine12
|
| • Comparing to remdesivir, less preclinical studies have been established for favipiravir to kill SARS-CoV-2 |
| • Currently, it was approved by the National Medical Products Administration of China as the first anti-COVID-19 drug in China, as the clinical trial had demonstrated efficacy with minimal side effects |
| Ivermectin |
Inhibiting the viral Protease |
• Anti-parasitic drug and was reported to inhibit both human immunodeficiency virus (HIV) and dengue virus13,14
|
| • A recent in vitro study has proven its capability to reduce the viral RNA of SARS-CoV-2 (ref. 1) |
| • Currently, establishing a safety profile is the next step to verify Ivermectin's ability for curing patients diagnosed with COVID-19 (ref. 15) |
| Lopinavir/ritonavir |
• Both are used in a combination protocol for the treatment of HIV |
| • Although coronaviruses encode a different enzymatic class of protease, a number of clinical and in vitro model studies have been completed using this combination on SARS and MERS viruses.16,17
|
| • Currently, both drugs are prescribed in a clinical trial in early-stage COVID-19; however, no benefit was observed beyond standard care18
|
| Hydroxychloroquine (HCQ) |
Blocking virus–cell membrane fusion |
• A well-known antimalarial and anti-autoimmune agent with basic character |
| • It blocks the viral infection of SARS-CoV-2 by altering the endosomal pH required for the membrane fusion between the virus and the host cell19 or by interfering in the glycosylation of its cellular receptor, ACE2 (ref. 20) |
| • It was approved in different countries to control the spread of COVID-19.21 However, larger randomized controlled trials are required for further evaluation22
|
| • On 17 June 2020, WHO announced that the use of HCQ in COVID-19 treatment was ceased |
| Umifenovir |
• It is a fully-functionalized indole with an antiviral activity against influenza infection. It directs hemagglutinin glycoprotein on the surface of the influenza virus and subsequently prevents its fusion with endosome after endocytosis |
| • Currently, it is undergoing trials for COVID-19 (ref. 23) |
| Lactoferrin (LTF) |
• It is a globular glycoprotein found in mammalian milk |
| • It acquires a wide spectrum of biological activities especially immunological properties |
| • In some countries e.g. Egypt, it has been prescribed in the protocol for the treatment of COVID-19 patients |
| • LF prevents coronavirus to get attached to Heparan Sulfate Proteoglycans (HSPGs) present at the surface of host cells as these viruses are considered to bind to the host cell by binding first to HSPGs24
|
| Recombinant human Angiotensin-converting enzyme 2-APN01(rhACE2) |
Preventing the inflammatory storm |
• It blocks S protein from interacting with cellular ACE2 and so inhibits SARS-CoV-2 replication |
| • The administration of rhACE2 can decrease the serum level of angiotensin II and so there was no further activation of ACE2 receptor |
| • Currently, a pilot study is now evaluating the role of rhACE2 in COVID-19 |
| Interleukin (IL)-6 inhibitors e.g. sarilumab, siltuximab, and tocilizumab |
• Interleukin (IL)-6, IL-1, and TNF-α are the most important pro-inflammatory cytokines in the human body |
| • Interleukin (IL) inhibitors may ameliorate severe damage to lung tissue caused by cytokine release in patients with serious SARS-CoV-2 infections. Several studies have indicated a “cytokine storm” with the release of IL-6, IL-1, IL-12, and IL-18, along with tumor necrosis factor-alpha (TNFα) and other inflammatory mediators. The increased pulmonary inflammatory response may result in increased alveolar-capillary gas exchange, making oxygenation difficult in patients with severe illness25,26
|
| Fingolimod |
• It is an immunomodulation drug, mostly used for treating multiple sclerosis27
|
| • It is a highly potent functional antagonist of S1P1 receptors in lymph node T cells |
| • Currently, it is under clinical trials for the treatment of SARS-CoV-2, NCT04280588, MRCTA, and ECFAH of FMU [2020]027 |
| Antibiotics as azithromycin |
• Known macrolide antibiotics |
| • Reduce viremia to zero when used in combination with other drugs |
| • Approved for hospitalized cases |
| Nitazoxanide28
|
• Orally active broad-spectrum antiparasitic |
| • Prodrug transformed rapidly to active metabolites, such as, tizoxanide and tizoxanide |
| • Known to potentiate interferon-alfa and interferon-beta assembly |
| • Previously revealed an in vitro activity against MERS-CoV and other coronaviruses |
| • Recommended in combination with azithromycin |
| Thalidomide |
• Thalidomide has been repurposed with different pharmacological effects |
| • It was reported as an anti-inflammatory drug as it prevents the synthesis of TNF-α,29 treating H1N1-infected mice by reducing pro-inflammatory cytokines30
|
| • Present studies are based on its immunomodulatory properties to treat COVID-19 (NCT04273529, NCT04273581), phase 2 |
