Table 1.
Proteases as targets for SARS-CoV-2 for the treatment of COVID-19.
| Target/Drug | Findings | References |
|---|---|---|
| RdRp | ||
| RDV | Blocking of viral infection in Vero cells | [26] |
| Reduced lung inflammation and viral titers in monkeys | [27] | |
| Shortened recovery time, reduced mortality rates for COVID-19 | [28,29] | |
| Approved for COVID-19 treatment in October 2020 | [30] | |
| FPV | Shortened treatment, improved chest CT compared to LPV/RPV | [31] |
| Significantly higher recovery rates in patients | [34] | |
| Clinical improvement in patients | [35] | |
| Improved viral clearance | [36] | |
| Approval in Russia, Bangladesh, Pakistan, Jordan, Egyp | [36] | |
| RBV | Anti-SARS-CoV-2 activity in Vero cells | [37] |
| Shortened time from treatment start to negative PCR test | [38] | |
| No improvement in negative conversion time or mortality | [39] | |
| Sofosbuvir | Shortened recovery, lower mortality in patients | [41,42] |
| No difference in hospitalization or number of deaths | [43] | |
| Galidesivir | No clinical benefit, clinical trial discontinued | [44] |
| EIDD-2810 (Molnupiravir) | Significantly reduced viral load in ferrets | [45] |
| Inhibition of SARS-CoV-2 in mice | [46] | |
| Clinical trials on safety, tolerability and efficacy in progress | [47,48] | |
| Reduced hospitalization risk in two phase I trials | [49] | |
| Approved in the UK and by the FDA in the US | [50] | |
| 3CLPro | ||
| Boceprevir | Inhibition of SARS-CoV, MERS-CoV and SARS-COV-2 in cell | [51] |
| Reduced SARS-CoV-2 RNA in Vero cells | [51] | |
| Ivermectin | Reduced SARS-CoV-2 transmission in non-severe COVID-19 | [52] |
| No difference in PCR positivity compared to placebo | [53] | |
| Meta-analysis showed no reduction in recovery time, mortality | [54] | |
| No clinical benefits compared to placebo in clinical trial | [55] | |
| Paxlovid | 89% reduced risk of hospitalization/death; FDA approval | [56] |
| PLPro | ||
| Nathalene | Inhibition of SARS-CoV-2 replication in Vero cells | [57] |
| GRL-0617 | Reduced viral infection in CaCo-2 cells | [58] |
| Helicase LPro I | ||
| Quercetin | IC50 of 8.1 μM against SARS-CoV helicase | [59] |
| 7-O-AMQ derivatives | IC50 of 2.7–5.2 μM against SARS-CoV helicase | [60] |
| Myricetin | IC50 of 2.71 μM against SARS-CoV helicase | [61] |
3CLpro, 3-chymotrypsin-like protease; 7-O-AMQ der, 7-O-arylmethylquercetin derivatives; FPV, favipiravir; LPV, lopanivir; PLpro. Papain-like protease; RdRp, RNA dependent RNA polymerase; RDV, remdesivir; RPV, ritonavir.