Mechanistic insights into the activity of SARS-CoV-2 RNA polymerase inhibitors using single-molecule FRET.

ABSTRACT: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in significant global mortality, with over 7 million cases reported. Despite extensive research and high vaccination rates, highly mutated forms of the virus continue to circulate. It is therefore important to understand the viral lifecycle and the precise molecular mechanisms underlying SARS-CoV-2 replication. To address this, we developed a single-molecule Förster resonance energy transfer (smFRET) assay to directly visualize and analyse in vitro RNA synthesis by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We purified the minimal replication complex, comprising nsp12, nsp7, and nsp8, and combined it with fluorescently labelled RNA substrates, enabling real-time monitoring of RNA primer elongation at the single-mo

SUBMITTER: Groves D 

PROVIDER: S-EPMC12038395 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature