Structural basis for substrate selection by the SARS-CoV-2 replicase.

ABSTRACT: The SARS-CoV-2 RNA-dependent RNA polymerase coordinates viral RNA synthesis as part of an assembly known as the replication-transcription complex (RTC)¹. Accordingly, the RTC is a target for clinically approved antiviral nucleoside analogues, including remdesivir². Faithful synthesis of viral RNAs by the RTC requires recognition of the correct nucleotide triphosphate (NTP) for incorporation into the nascent RNA. To be effective inhibitors, antiviral nucleoside analogues must compete with the natural NTPs for incorporation. How the SARS-CoV-2 RTC discriminates between the natural NTPs, and how antiviral nucleoside analogues compete, has not been discerned in detail. Here, we use cryogenic-electron microscopy to visualize the RTC bound to each of the natural NTPs in sta

SUBMITTER: Malone BF 

PROVIDER: S-EPMC9891196 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature