Does remdesivir exert high selective pressure for escape mutations in the SARS-CoV-2 RNA Dependent RNA Polymerase?
SARS-CoV-2 RdRp remains a highly conserved drug target, and remdesivir does not appear to exert high selective pressure for escape mutations.
(Tajima's D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.
Mari et al. (Wed,) studied this question.