Table 1. Compounds with possible anti-SARS-CoV-2 activity based on in vitro studies, virtual screening, or in silico studies.
| Drug | Drug target/drug class | Mechanism | Reference(s) | |
|---|---|---|---|---|
| Nelfinavir | SARS-CoV-2 main protease (Mpro) | Inhibition of the viral protease enzyme | [185] | |
| HTCC polymer a | Spike protein | Blocks interaction of spike protein with cellular receptor | [186] | |
| Theaflavin | Receptor binding domain (RBD) | Binds to the RBD of spike protein preventing viral entry | [187] | |
| Dipyridamole | SARS-CoV-2 Mpro | Inhibitor of Mpro and NF-κB signaling pathway | [188] | |
| Niclosamide | SKP2 | Inhibition of SKP2 activity thereby enhancing autophagy and reduces replication | [189, 190] | |
| Ciclesonide | Viral riboendonuclease NSP15 | Blocks replication of SARS-CoV-2 (direct-acting antiviral) and its anti-inflammatory activity | [190, 191] | |
| EIDD-2801 b | Ribonucleoside analog | Lethal mutagenesis causes the accumulation of deleterious transition mutations in the viral RNA | [192, 193] | |
| 3’-fluoro-3’-deoxythymidine triphosphate c | RNA-dependent RNA polymerase (RdRp) | Gets incorporated into SARS-CoV RdRp and terminates further polymerase extension. | [194] | |
| 3’-azido-3’-deoxythymidine triphosphate d | RdRp | Gets incorporated into SARS-CoV RdRp and terminates further polymerase extension. | [194] | |
| CVL218 | N-terminal domain of nucleocapsid (N) protein | Inhibits SARS-CoV-2 replication (antiviral) and suppress the CpG-induced IL-6 production (anti-inflammatory) | [195] | |
| Atazanavir | RdRp, Helicase, 3'-to-5' exonuclease , 2'-O-ribose methyltransferase, and endoRNAse | Inhibits the subunits of SARS-CoV-2 replication complex thereby inhibiting viral replication | [196] | |
| Prulifloxacin | Viral main protease (Mpro) | Inhibits viral replication and proliferation | [197] | |
| Tegobuvir | Viral main protease (Mpro) | Inhibits viral replication and proliferation | [197] | |
| Bictegravir | Viral main protease (Mpro) and 2′-O-ribose methyltransferase (2′-O-MTase) | Inhibits viral replication and proliferation | [36, 197] | |
| Sofosbuvir | RNA-dependent RNA polymerase (RdRp) | Binds to RdRp and inhibits further RNA chain extension thereby halting RNA replication. | [198] | |
| Camostat mesylate | Transmembrane serine protease family member II (TMPRSS2) | Blocks SARS-CoV-2 entry into the host cell | [120] | |
| Velpatasvir | 3C-like protease (3CLpro) | Inhibits viral replication and proliferation | [199] | |
| Ledipasvir | 3C-like protease (3CLpro) | Inhibits viral replication and proliferation | [199] | |
| Colistin | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Valrubicin | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Icatibant | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Bepotastine | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Epirubicin | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Epoprostenol | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Vapreotide | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Aprepitant | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Caspofungin | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Perphenazine | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [200] | |
| Selamectin | Unknown | Unknown | [201] | |
| Mefloquine hydrochloride | Unknown | Unknown | [201] | |
| Eravacycline | SARS-CoV-2 protease | Inhibits SARS-CoV-2 replication | [202] | |
| Valrubicin | SARS-CoV-2 protease | Inhibits SARS-CoV-2 replication | [202] | |
| Elbasvir | SARS-CoV-2 protease | Inhibits SARS-CoV-2 replication | [202] | |
| Ebselen | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [203] | |
| Saquinavir | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [204] | |
| Beclabuvir | SARS-CoV-2 Mpro | Inhibits SARS-CoV-2 replication | [204] | |
| Isoniazid pyruvate | Spike protein-ACE2 receptor complex | Limits binding of SARS-CoV-2 spike protein with ACE2 receptor | [205] | |
| Nitrofurantoin | Spike protein-ACE2 receptor complex | Limits binding of SARS-CoV-2 spike protein with ACE2 receptor | [205] | |
| Eriodictyol | Spike protein-ACE2 receptor complex | Limits binding of the SARS-CoV-2 spike protein with ACE2 receptor | [205] | |
| Cepharanthine | Virus spike protein host recognition domain | Disrupts the host-virus interactions | [205] | |
| Ergoloid | Virus spike protein host recognition domain | Disrupts the host-virus interactions | [205] | |
| Hypericin | Virus spike protein host recognition domain | Disrupts the host-virus interactions | [205] | |
| Carfilzomib | SARS-CoV-2 3C-like proteinase (3CLpro) | Inhibits SARS-CoV-2 replication | [206] | |
| Thymopentin | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [206] | |
| Ivermectin | Impα/β1 heterodimer | Destabilizes Impα/β1 heterodimer and prevents its binding to the viral protein thereby preventing it from entering the nucleus leading to more efficient antiviral response | [170] | |
| Grazoprevir | SARS-CoV-2 papain-like protease (PLpro) | Inhibits SARS-CoV-2 replication | [207] | |
| Telaprevir | SARS-CoV-2 PLpro | Inhibits SARS-CoV-2 replication | [207] | |
| Boceprevir | SARS-CoV-2 PLpro | Inhibits SARS-CoV-2 replication | [207] | |
| Mycophenolic acid | SARS-CoV-2 PLpro | Inhibits SARS-CoV-2 replication | [207] | |
| Cyclosporin A | Cyclophilin A (CypA) | CypA inhibitor (CypA is essential for replication) | [39] | |
| Cefuroxime | RdRp | Inhibits SARS-CoV-2 RdRp | [208] | |
| Tenofovir | RdRp | Inhibits SARS-CoV-2 RdRp | [208] | |
| Setrobuvir | RdRp | Inhibits SARS-CoV-2 RdRp | [208] | |
| Andrographolide | SARS-CoV-2 main protease (Mpro) | Inhibits SARS-CoV-2 replication | [209] | |
| Dolutegravir | 2′-O-ribose methyltransferase (2′-O-MTase) | Inhibits 2′-O-MTase (Inhibiting methylation of ribose 2′-O position of first and second nucleotide of viral mRNA, which sequesters it from host immune system) | [36] | |
| Paritaprevir | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [36] | |
| Raltegravir | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [36] | |
| GC373 | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [210] | |
| GC376 | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [210] | |
| Boceprevir | SARS-CoV-2 3CLpro | Inhibits SARS-CoV-2 replication | [211] | |
| Tretinoin | SARS-CoV-2 E protein ion channel | Inhibitors of ion channels formed by SARS-CoV-2 E protein and virus assembly Inhibitor | [212] | |
| Sovaprevir | SARS-CoV-2 receptor-binding domain (RBD) | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Elbasvir | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Grazoprevir | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Hesperidin | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Pamaqueside | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Diosmin | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] | |
| Sitogluside | SARS-CoV-2 RBD | Binds to RBD of spike protein, prevents viral entry | [213] |
aN-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride, bβ-d-N4-Hydroxycytidine (NHC), cActive triphosphate forms of alovudine, dActive triphosphate forms of azidothymidine