Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro.

ABSTRACT: SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is the key enzyme required for viral replication and mRNA synthesis. RdRp is one of the most conserved viral proteins and a promising target for antiviral drugs and inhibitors. At the same time, analysis of public databases reveals multiple variants of SARS-CoV-2 genomes with substitutions in the catalytic RdRp subunit nsp12. Structural mapping of these mutations suggests that some of them may affect the interactions of nsp12 with its cofactors nsp7/nsp8 as well as with RNA substrates. We have obtained several mutations of these types and demonstrated that some of them decrease specific activity of RdRp in vitro, possibly by changing RdRp assembly and/or its interactions with RNA. Therefore, natural polymorphisms in RdRp may potentially affect

SUBMITTER: Miropolskaya N 

PROVIDER: S-EPMC9568283 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature