Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment.
No clinical data are available on the development of SARS-CoV-2 resistance to remdesivir. The cell culture development of SARS-CoV-2 resistance to remdesivir has not been assessed to date.
Cell culture resistance profiling of remdesivir using the rodent CoV murine hepatitis virus identified 2 substitutions (F476L and V553L) in the viral RNA-dependent RNA polymerase at residues conserved across CoVs that conferred a 5.6 fold reduced susceptibility to remdesivir. The mutant viruses showed reduced viral fitness in cell culture and introduction of the corresponding substitutions (F480L and V557L) into SARS-CoV resulted in 6-fold reduced susceptibility to remdesivir in cell culture and attenuated SARS-CoV pathogenesis in a mouse model.