Evaluation of SARS-CoV-2 genomic mutations potentially conferring resistance to antiviral drugs in viral populations isolated from untreated SARS-CoV-2-infected subjects.

The development of safe and effective antiviral drugs was a crucial topic since the outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) global pandemic. The prevalence of SARS-CoV-2 variants and the genetic variability of the RdRp complex subunits and Nsp5 in SARS-Cov-2 populations isolated from a large series of subjects naïve to antiviral therapy were analyzed by new generation sequencing (NGS) techniques. Results showed that both nsp12 and nsp5, that has been targeted by antiviral therapies, may accumulate several naturally selected aa substitutions, which may potentially affect antiviral drug efficiency. Results also showed that ssp7 and nsp8 might be considered as new potential target for the development of new antiviral drugs because of their low genetic variability and essential role in SARS-CoV-2 replication.