Table 2.
Amino acid substitutions associated with reduced susceptibility to drugs with anti-coronavirus activity in in vitro model and by homology modeling.
| Antiviral drug | Drug-resistance mutationa | Corresponding residue in SARS-CoV-2b | Fold Change in EC50c | References |
|---|---|---|---|---|
| RdRp | ||||
| Remdesivir | F476LMHV | F480 | 2.4 | Agostini et al. (2018) |
| V553LMHV | V557 | 5 | ||
| F476LMHV+V553LMHV | F480+V553 | 5.6 | ||
| F480LSARS-CoV-1+V557LSARS-CoV-1 | F480+V557 | 6 | ||
| 5-FU | V553IMHV | V557 | n.a. | Sexton et al. (2016) |
| M611FMHV | M615 | n.a. | ||
| 5-AZC | V553IMHV | V557 | n.a | |
| Ribavirin | G64SPV | N459 | n.a. | Neogi et al. (2020) |
| L420APV | D865 | n.a. | ||
| Favipiravir | K159RCVB3 | K545 | n.a. | |
| 3CL-PR | ||||
| GRL-001 | T26IMHV | T26 | 3.06c | Deng et al. (2014) |
| D65GMHV | N65 | 2.56c | ||
| T26IMHV + D65GMHV | T26+N65 | >6c | ||
| T26IMHV + A298DMHV | T26+S301 | >6c | ||
| GC376 | N25SFel-Cov | T25 | 1.38 | Perera et al. (2019) |
| A252SFel-Cov | A255 | 1.15 | ||
| K260NFel-Cov | D263 | 1.05 | ||
| N25SFel-Cov + K260NFel-Cov | T25+D263 | 1.53 | ||
| N25SFelCov + A252SFelCov + K260NFel-Cov | T25+A255+D263 | 1.68 | ||
Abbreviations: RdRp, RNA-dependent RNA polymerase; 5-FU, 5-fluorouracil; 5-AZC, 5-azacytidine; 3CL-PR, 3CL protease; MHV, murine hepatitis virus; SARS-CoV-1, severe acute respiratory syndrome coronavirus; PV, poliovirus; CVB3, Coxsackievirus B3; FelCov, feline coronavirus.
The column reports the drug-resistance mutations identified for each antiviral drug. The virus in which the mutation has been identified is reported as subscript.
For each drug-resistance mutation, the corresponding residue in SARS-CoV-2 RdRp and 3CL-PR has been determined basing on homology of SARS-CoV-2 sequences with MHV and SARS-CoV-1 sequences.
The fold change in EC50 was calculated basing on the EC50 value of the mutant and EC50 value of wild-type reported in Reference #4.