Table 1.

Current therapeutic drugs used to treat COVID-19.

Drug	Description and mechanism of action	References
Inhibitors of the cellular entry of SARS-CoV-2
Chloroquine and Hydroxychloroquine (QuensylTM, PlaquenilTM, HydroquinTM, DolquineTM, QuinoricTM)	• Antimalarial; they have been used for decades for the prophylaxis and treatment of malaria and for various autoimmune diseases • Inhibit the terminal phosphorylation of ACE2 and elevate the pH in endosomes. • Chloroquine can inhibit the entry of SARS-CoV-2 and prevent virus-cell fusion by interfering with glycosylation of the ACE2 receptor and its binding with the spike protein, suggesting that chloroquine treatment might be more effective in the early stage of infection before COVID-19 reduces ACE2 expression and activity. • Hydroxychloroquine exhibits an anti-inflammatory effect on Th17-related cytokines (IL-6, IL-17, and IL-22) in healthy individuals and systemic lupus erythematosus and rheumatoid arthritis patients.	(18–21)
Camostat mesylate (FoipanTM)	• Developed decades ago for the treatment of oral squamous cell carcinoma, dystrophic epidermolysis, exocrine pancreatic enzyme inhibition, and chronic pancreatitis • TMPRSS2 protease activity as a synthetic serine protease inhibitor. In a clinical trial investigating the effects of camostat mesylate against dyspepsia associated with non-alcoholic mild pancreatic disease, 95 patients received 200 mg camostat mesylate three times daily for 2 weeks and showed only mild side effects and no severe adverse effects.	(22–24)
Nafamostat mesylate (BuipelTM)	• Approved in Japan for the treatment of acute pancreatitis, disseminated intravascular coagulation and for anticoagulation in extracorporeal circulation • TMPRSS2 protease activity: clinically proven as a synthetic serine protease inhibitor. Nafamostat mesylate has been shown to inhibit MERS-CoV S protein-mediated viral membrane fusion with TMPRSS2-expressing lung Calu-3 host cells by inhibiting TMPRSS2 protease activity. It may also inhibit the cellular entry of SARS-CoV-2. In cell culture experiments with simian Vero E6 cells infected with SARS-CoV-2, Nafamostat mesylate was shown to inhibit SARS-CoV-2 infection at an EC50 of 22.50 μM.	(19, 25, 26)
Monoclonal antibodies targeting SARS-CoV entry
80R, F26G19, m396, CR3014, CR3022, F26G18, m396, 201, S230	• Binds to the conformational epitope on the S1 fragment of SARS-CoV or to the amino acid residues with high affinity on the S1 fragment of SARS-CoV. • Blocks the interaction of the S1 subunit protein with the cellular receptor ACE2	(27–32)
Inhibitors of the replication, membrane fusion, and assembly of SARS-CoV-2
Remdesivir	• A novel small-molecule adenine nucleotide analog antiviral drug synthesized and developed by Gilead Sciences in 2017 that has shown efficacy against Ebola virus in rhesus monkeys. It displays antiviral activity against other single-stranded RNA viruses, including filoviruses, pneumoviruses, paramyxoviruses, and the coronaviruses MERS-CoV and SARS-CoV. • It results in the delayed chain cessation of nascent viral RNA. It potently blocks SARS-CoV-2 infection at a low range of micromolar concentrations and has a high selectivity index with an EC50 of 0.77 μM and a CC50 > 100 μM. It acts early in infection and is metabolized into its active form GS-441524, which is an adenine nucleotide analog that interferes with the activity of viral RNA polymerase and that promotes the evasion of proofreading by viral exoribonuclease, leading to the inhibition of viral RNA synthesis.	(19, 33, 34)
Lopinavir/ritonavir (KaletraTM)	• Lopinavir was developed in 1998 to circumvent HIV resistance toward the protease inhibitor ritonavir. The combination of lopinavir and ritonavir was first established as an effective oral drug for the treatment of HIV-infected individuals when used in combination with other antiretroviral agents. • Lopinavir-ritonavir administration significantly decreased coronavirus titres, and low or no coronavirus titres were observed in the follow-up study. Another study investigated lopinavir in patients with COVID-19 receiving either lopinavir-ritonavir 400 mg/100 mg orally twice daily plus the standard of care or the standard of care alone.	(35)
Umifenovir (ArbidolTM)	• A small indole-derivate molecule licensed for oral prophylaxis and treatment of infections with influenza A and B viruses and other respiratory viruses that has been demonstrated to inhibit in vitro infection with globally prevalent pathogenic viruses, including the hepatitis C virus, hepatitis B virus, Ebola virus, Lassa virus, human herpesvirus, poliovirus, and vesicular stomatitis virus. • Prevents viral host cell entry by inhibiting membrane fusion of the viral envelope and the host cell cytoplasmic membrane via inhibition of clathrin-mediated endocytosis, thereby preventing virus infection.	(36)
Favipiravir (AviganTM)	• An oral pyrazinecarboxamide derivative and guanine analog. • Selectively and potently inhibits the RNA-dependent RNA polymerase (RdRP) of RNA viruses (influenza A virus, flavi-, alpha-, filo-, bunya-, arena-, and noroviruses as well as West Nile virus, yellow fever virus, foot-and-mouth-disease virus, Ebola virus and Lassa virus) and induces lethal RNA transversion mutations, thereby producing a nonviable virus phenotype. A study showed favipiravir has efficacy in Vero E6 cells infected with SARS-CoV-2 with an EC50 of 61.88 μM and a CC50 over 400 μM.	(19)
Anti-cytokines and chemokines
TocilizumabSarilumabSiltuximab	• Anti-IL-6 receptor is a human immunoglobulin G1 monoclonal antibody (mAb) that binds specifically to both soluble and membrane-bound interleukin-6 receptors (IL-6Rs) • Blocks the interaction between the cytokine and its receptor, avoiding the amplification of inflammation associated with lung injury that leads to respiratory distress.	(37, 38)
Supporting agents
Azithromycin	• An antibiotic that can be used for different types of bacterial infections, such as respiratory and skin infections and sexually transmitted diseases. It has been proven to be active against the Zika and Ebola viruses and to prevent severe respiratory tract infections when used to treat patients suffering from viral infection. It has been used as an adjunctive therapy to provide antibacterial coverage and exerts potential immunomodulatory and anti-inflammatory effects in the treatment of some viral respiratory tract infections (e.g., influenza). • Prevents the growth of bacteria by interfering with bacterial protein synthesis. It binds to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. In COVID-19 patients, Gautret et al. reported 100% viral clearance based on nasopharyngeal swabs in six patients who were co-treated with hydroxychloroquine and azithromycin. However, Molina et al. reported findings that contrasted with those reported by Gautret. Based on those results, the data presented to date are insufficient to evaluate the possible clinical benefits of azithromycin in patients with COVID-19	(39, 40)
Corticosteroids	• A potent anti-inflammatory and anti-fibrotic drug. • Low doses of methylprednisolone prevent extended cytokine release and may accelerate the resolution of pulmonary and systemic inflammation in pneumonia. Recently, many medical researchers have stated that corticosteroids may improve the dysregulated immune response caused by sepsis (a possible complication of infection with COVID-19) and increase the blood pressure when it is low. In a retrospective cohort study, 201 patients with confirmed COVID-19 who developed ARDS were treated with methylprednisolone (1–2 mg/kg daily via IV for 5–7 days), and the results showed that treatment with methylprednisolone may be beneficial for patients who develop ARDS in terms of the reduction of the risk of death.	(41)