Table 3.

List of agents that are being repurposed as therapeutic agents against SARS-CoV-2

Drug	Indications	Mechanism of action	Possible action on SARS-CoV-2
Chloroquine	1. Malarial parasite infection and amebicide. 2. Rheumatoid arthritis.	Elevates endosomal pH and interferes with ACE-2 glycosylation.	1. It is known to block receptors of SARS- CoV-2. 2. It has an immune-modulating activity and targets the endosome/ACE-2 receptor [37, 38].
Remdesivir (RDV)	1. Ebola 2. SARS-CoV 3. MERS-CoV	A nucleotide analogue that blocks viral nucleotide synthesis to stop viral replication. The likely mechanism of action is delayed RNA chain termination.	It can inhibit replication of a wide variety of coronaviruses by blocking the RNA dependent RNA polymerase required for replication [39–41].
Hydroxychloroquine	1. Malaria 2. Rheumatoid arthritis 3. Discoid, or systemic lupus and erythematosus.	It is a disease-modifying anti-rheumatic drug. It regulates activity of immune system, which may be overactive in some conditions.	It can modify underlying disease process, rather than simply treating the symptoms [42, 43].
Ritonavir	1. Human immunodeficiency virus (HIV) 2. SARS-CoV-2	It prevents cleavage of the gag-pol polyprotein, which results in non-infectious, immature viral particles. It is a potent inhibitor of cytochrome P450, and CYP3A4 isoenzyme, found in the intestinal tract and liver. It is a type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to heme iron via thiazole nitrogen, which decreases redox potential of protein and averts its reduction with the redox partner, cytochrome P450 reductase.	It can inhibit the viral protease and activates the nuclear receptor subfamily-1 [44, 45].
Chlorpheniramine	1. A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. Also used in veterinary applications. One of the most widely used classical antihistaminic.	It can bind to the histamine H1 receptor. This blocks the action of endogenous histamine, which leads to temporary relief from the negative symptoms of histamine.	It works by blocking the action of histamine, a substance in the body that causes allergic reactions likely to reduce inflammation. [46–49].
Lopinavir–Ritonavir	1. Usually prescribed with HIV medication to boost immunity of a patient.	Both Lopinavir and Ritonavir belong to a class of drugs known as HIV protease inhibitors. Ritonavir boosts the levels of Lopinavir.	The randomized trial found that Lopinavir-Ritonavir treatment added to standard supportive care was not associated with clinical improvement or mortality in seriously ill patients with COVID-19 infection as compared to standard care alone [50, 51].
Oseltamivir	1. Influenza viruses A (including pandemic H1N1) and B.	It inhibits activity of the viral neuraminidase enzyme found on the surface of virus, which prevents budding from the host cell, viral replication, and infectivity.	It has been recommended by WHO for people at high risk of infection before or after exposure to pandemic influenza. May reduce COVID-19 transmission [52].
Lopinavir	1. Approved drug combination for HIV.	It is a protease inhibitor that may inhibit the viral proteases 3CLpro or PLpro.	It is currently under investigation in combination with Ritonavir for the treatment of COVID-19 treatment [53–55].
Rifampin	1. A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium.	It inhibits DNA-dependent RNA polymerase, leading to suppression of RNA synthesis and cell death.	It suppresses initiation of RNA synthesis. It is bactericidal and acts on both intracellular and extracellular organisms. Under trail for COVID-19 [56–59].
Baricitinib	1. Rheumatoid arthritis	Blocks action of JAK1/2, and disrupts activation of downstream signalling molecules and pro-inflammatory mediators.	It inhibits tyrosine-protein kinase JAK1, JAK2, JAK3, protein-tyrosine kinase 2-beta, which can interfere with inflammatory process [60, 61].
Darunavir	1. HIV 2. SARS-CoV-2 (under clinical trials)	It is an HIV protease inhibitor, prevents HIV replication by binding to the enzyme, stops the dimerization and catalytic activity of HIV-1 protease. In particular, it inhibits cleavage of HIV encoded Gag-Pol proteins in cells that have been infected with the virus, halting formation of mature virus particles. Primary active site amino acids (Asp-29 and Asp-30) on the protease likely contribute to its potency and efficacy against resistant variants of HIV-1.	It is being studied as a possible treatment for SARS-CoV-2 due to in vitro evidence supporting its ability to combat this infection. Clinical trials are underway and are expected to conclude by August 2020 [62].
Favipiravir (also known as Avifavir)	1. Influenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A)	The active Favipiravir-RTP selectively inhibits RNA polymerase and prevents replication of viral genome.	It has been investigated for treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now SARS-CoV-2. It is recently approved by the Russian government for COVID-19 treatment [63–65].
Galidesivir	1. Ebola 2. Marburg 3. Yellow Fever 4. Zika viruses	It works by inhibiting the nucleotides binding site on viral RNA polymerase, leading to a structural change in the enzyme due to altered electrostatic interactions. Disruption of viral RNA polymerase activity results in premature termination of the elongating RNA strand.	It inhibits the “RNA-directed RNA polymerase L” action [66].
Umifenovir	1. Herpes simplex virus 2. Hepatitis B virus 3. Hepatitis C Virus 4. SARS-CoV-2 5. Zika virus 6. Lassa mammarenavirus 7. Chikungunya virus 8. Coxsackievirus B5 9. Reovirus species 10. Hantaan orthohantvirus 11. Ebola virus	It is considered as direct-acting antiviral due to virucidal effects and a host-targeting agent due to effects on one or multiple stages of the viral life cycle (e.g. attachment, internalization). It targets the S protein and the ACE2 receptor.	It is being investigated as a potential treatment and prophylactic agent for COVID-19 in combination with both currently available and investigational HIV therapies [67–70].
Nitazoxanide	1. Anti-Helminthic 2. Anti-Protozoal 3. Viral infection-induced diarrhoea	It induces lesions in cell membrane and depolarizes mitochondrial membrane by inhibiting quinone oxidoreductase (NQO1), nitroreductase-1 and protein disulphide isomerase enzymes.	A drug that may inhibit viral protein expression [73].