TABLE 1.

Representative direct-acting antivirals for CoV infections.

Name of drugs	Mechanism of action	In vitro	In vivo	Clinical trial	Approved	References
EK1C4	Mediates membrane fusion by targeting the 6-HB of HIV and the HR1 domain in divergent human coronaviruses	HIV, SARS-CoV-2	HIV, SARS-CoV-2	N.A.	N.A.	Xia et al., 2020a
Arbidol	Impedes spike trimerization	Influenza, HBV, HCV, CHIKV, RSV, reovirus, Hantaan virus, coxsackie virus B5 ZIKV, SARS-CoV-2	Influenza, SARS-CoV, SARS-CoV-2	Influenza, SARS-CoV, SARS-CoV-2	Influenza	Blaising et al., 2014; Nojomi et al., 2020; Vankadari, 2020
Viral RNA: Nucleoside/nucleotide analogs
Favipiravir	Incorporates into the genome of RNA viruses to interrupt viral RNA synthesis by blocking RdRp activity	Influenza, EBOV, MARV, YFV, RVFV JUNV, LASV, CCHFV, CHIKV, WNV, norovirus and enterovirus, arenaviruses, Nipah virus, SARS-CoV-2	Influenza, Ebola, SARS-CoV-2	Ebola,SARS-CoV-2	Influenza	Sissoko et al., 2016; Furuta et al., 2017; de Clercq, 2019
Ribavirin	Incorporates into the genome of RNA viruses to interrupt viral RNA synthesis by blocking RdRp activity	HCV, RSV, SARS-CoV, MERS-CoV, SARS-CoV-2, viral haemorrhagic fevers	HCV, RSV, SARS-CoV, MERS-CoV, SARS-CoV-2	HCV, RSV, SARS-CoV, MERS-CoV, SARS-CoV-2	HCV, RSV	Zumla et al., 2016
Remdesivir	Incorporates into the genome of RNA viruses to interrupt viral RNA synthesis by blocking RdRp activity	Bat CoVs, SARS-CoV, MERS-CoV, SARS-CoV-2	Bat CoVs, SARS-CoV, MERS-CoV, SARS-CoV-2	SARS-CoV, and MERS-CoV, SARS-CoV-2	HIV, Ebola, SARS-CoV-2	Warren et al., 2016; Sheahan et al., 2017; Mulangu et al., 2019; Caly et al., 2020; Wang et al., 2020c
Galidesivir	Incorporates into the genome of RNA viruses to interrupt viral RNA synthesis by blocking RdRp activity	ZIKV SARS-CoV MERS- CoV SARS-CoV-2	ZIKV SARS- CoV MERS- CoV SARS-CoV-2	Yellow fever, SARS- CoV, MERS-CoV, SARS-CoV-2	HCV	Elfiky, 2020; Lim et al., 2020
EIDD-2801	Incorporates into the genome of RNA viruses to interrupt viral RNA synthesis by blocking RdRp activity	SARS-CoV-2	SARS- CoV, MERS- CoV, SARS-CoV-2	EIDD-2801	N.A.	Sheahan et al., 2020; Wahl et al., 2021
Viral enzyme: protease inhibitors
Disulfiram	Inhibits Papain-like protease	MERS SARS, SARS-CoV-2	N.A.	N.A.	Alcohol dependence	Lin et al., 2018; Ma et al., 2020
Lopinavir- ritonavir	Inhibits 3 chymotrypsin-like protease	SARS-CoV, MERS-CoV, SARS-CoV-2 HCoV-229E, HCoV-NL63, animal CoVs	SARS-CoV, MERS-CoV, SARS-CoV-2, HCoV-229E, HCoV-NL63, animal CoVs	SARS-CoV, MERS-CoV, SARS-CoV-2	HIV	Zumla et al., 2016; Cao B. et al., 2020
Darunavir	Inhibits dimerization of HIV-1 protease	SARS-CoV-2	N.A.	SARS-CoV-2	HIV1	Chen J. et al., 2020; WHO Solidarity Trial Consortium et al., 2021
N3	Inhibits Mpro	SARS-CoV-2	N.A.	N.A.	N.A.	Jin et al., 2020b
11a/11b	Inhibits Mpro	SARS-CoV-2	SARS-CoV-2	N.A.	N.A.	Dai et al., 2020
Carmofur	Inhibits Mpro	SARS-CoV-2	N.A.	N.A.	N.A.	Jin et al., 2020c

EBOV, Ebola virus, MARV, Marburg virus, dengue virus, JUNV, Junin virus, CCHFV, Crimean-Congo hemorrhagic fever virus, RVFV, Rift Valley fever virus, LASV, Lassa virus, YFV, yellow fever virus, RSV, respiratory syncytial virus, CHIKV, Chikungunya virus.