Table 1.
Therapeutic candidates for COVID-19.
| Class | Drug | Antiviral effect | ||
|---|---|---|---|---|
| In vitro | In vivo | RCT | ||
| Polymerase inhibitor | Ribavirin | EC50 = 109.50 μM, CC50 > 400 μM, SI > 3.65; MOI = 0.05, 48 hpi, Vero E6 (12) | N/A | IFN-β1b (subcutaneous), LPV/r, ribavirin: faster viral clearance and reduced inflammatory response (13) |
| Favipiravir | EC50 = 61.88 μM, CC50 > 400 μM, SI > 6.46; MOI = 0.05, 48 hpi, Vero E6 (12) | Modest reduction of viral load in hamsters (14) | Higher recovery rate and faster viral clearance in moderate COVID-19 (15, 16); cannot rescue severe COVID-19 (16) Approval in China, Russia, and India (17) |
|
| Remdesivir | EC50 = 0.77 μM, CC50 > 100 μM, SI > 129.87; MOI = 0.05, 48 hpi, Vero E6 (12) | Improved clinical outcome in rhesus macaques (20) | Shorter time to recovery (18); few clinical benefits in severe COVID-19 (19) US FDA approval in hospitalized patients (21) |
|
| Sofosbuvir & HCV NS5A inhibitors |
Sofosbuvir: EC50 = 6.2 μM, CC50 = 381 μM, SI = 61; MOI = 0.1, 48 hpi, Huh-7 (23) EC50 = 9.5 μM, CC50 = 512 μM, SI = 54; MOI = 0.1, 48 hpi, Calu-3 (23) Daclatasvir: EC50 = 0.8 μM, CC50 = 31 μM, SI = 39; MOI = 0.01, 24 hpi, Vero (23) EC50 = 0.6 μM, CC50 = 6.1 μM, SI = 47; MOI = 0.1, 48 hpi, Huh-7 (23) EC50 = 1.1 μM, CC50 = 3.0 μM, SI = 34; MOI = 0.1, 48 hpi, Calu-3 (23) |
N/A |
Sofosbuvir/daclatasvir: faster recovery and lower mortality (22) Sofosbuvir/velpatasvir: in progress |
|
| Protease inhibitor | Boceprevir | EC50 = 1.31 μM, CC50 >100 μM, SI > 76.3; 60 TCID50, 5 dpi, Vero 76 (24) | N/A | N/A |
| α-ketoamide (compound 13b)* | EC50 = 4~5 μM, CC50 unknown; MOI = 0.05, Calu-3 (25) | N/A | N/A | |
| Peptidomimetic aldehydes 11a & 11b* |
11a: EC50 = 0.53 μM, CC50 > 100 μM, SI > 189; MOI = 0.05, 24 hpi, Vero E6 (26) 11b: EC50 = 0.72 μM, CC50 > 100 μM, SI > 139; MOI = 0.05, 24 hpi, Vero E6 (26) |
N/A | N/A | |
| GC-376* | EC50 = 3.37 μM, CC50 >100 μM, SI > 29.7; 60 TCID50, 5 dpi, Vero 76 (24) | N/A | N/A | |
| Calpain inhibitors* |
Calpain inhibitor II: EC50 = 2.07 μM, CC50 >100 μM, SI > 48.3; 60 TCID50, 5 dpi, Vero 76 (24) Calpain inhibitor XII: EC50 = 0.49 μM, CC50 >100 μM, SI > 204; 60 TCID50, 5 dpi, Vero 76 (24) |
N/A | N/A | |
| Lopinavir/ Ritonavir (LPV/r) |
EC50 = 26 μM, CC50 = 49.75 μM, SI = 1.9; MOI = 0.02, 48 hpi, Vero E6 (29) | Lower clinical scores but no effect on viral titers in ferrets (30) | No clinical benefits (27, 28) | |
| Darunavir/ Cobicistat (DRV/c) |
EC50 >100 μM (inactive), CC50 >100 μM; MOI = 0.01, 48 hpi, Caco-2 (32) | N/A | No impact on viral clearance (31) | |
| Host-targeting agent | Interferons (IFNs) |
IFN-α A/D (pretreatment): EC50 = 1.35 IU/ml; MOI = 0.01, 22 hpi, Vero (33) IFN-β1a (pretreatment): EC50 = 0.76 IU/ml; MOI = 0.01, 22 hpi, Vero (33) IFN-β1a (posttreatment): EC50 = 1.971 IU/ml; MOI = 0.001, 48 hpi, Vero E6 (35) IFN-β1 (2,000 IU/ml) & IFN-λ (300 ng/ml): Prevented infection in T84 & Caco-2 (37) |
N/A |
IFN-α2b (aerosol): Faster viral clearance and reduced inflammatory response (34) IFN-β1b (subcutaneous), LPV/r, ribavirin: Faster viral clearance and reduced inflammatory response (13) IFN-β1a (subcutaneous): Increased discharge rate and decreased mortality in severe COVID-19 (36) IFN-κ (aerosol) plus TFF2: Faster recovery, viral clearance, and discharge (38) IFN-λ: In progress |
| Serine protease inhibitors |
Camostat: EC50 = 87 nM, entry in Calu-3 (39) Nafamostat: EC50 = 5 nM, entry in Calu-3 (39) |
N/A | In progress | |
| Dexamethasone | N/A | N/A | Lower mortality in COVID-19 patients who required respiratory support (40) | |
| Losartan | N/A | N/A | In progress | |
| Chloroquine (CQ)/Hydroxychloroquine (HCQ) |
CQ: Inactive in Calu-3 cells (43) EC50 = 2.71/3.81/7.14/7.36 μM, CC50 = 273.20 μM, SI = 100.81/71.71/38.26/37.12; MOI = 0.01/0.02/0.2/0.8, 48 hpi, Vero E6 (44) EC50 = 1.13 μM, CC50 > 100 μM, SI > 88.50; MOI = 0.05, 48 hpi, Vero E6 (12) EC50 = 5.47 μM; MOI = 0.01, 48 hpi, Vero (46) HCQ: EC50 = 4.51/4.06/17.31/12.96 μM, CC50 = 249.50 μM, SI = 55.32/61.45/14.41/19.25; MOI = 0.01/0.02/0.2/0.8, 48 hpi, Vero E6 (44) EC50 = 0.72 μM; MOI = 0.01, 48 hpi, Vero (46) |
CQ: N/A HCQ: Lower clinical scores but no effect on viral titers in ferrets (30) No antiviral activity in hamsters (14, 45) No antiviral activity in macaques (45, 47) |
No clinical benefits (41, 42) | |
| Arbidol | EC50 = 4.11 μM, CC50 = 31.79 μM, SI = 7.73; MOI = 0.05, 48 hpi, Vero E6 (49) | N/A | No clinical benefits (48) | |
N/A, not available; RCT, randomized controlled trial.
*SARS-CoV-2 Mpro inhibitors.