Xinzhou Xu

Abstract Nucleoside analogues (NuAs) targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) represent a key antiviral strategy. However, their efficacy is fundamentally limited by the viral proofreading exoribonuclease nsp14, which excises misincorporated NuAs from nascent viral RNA.

Abstract Understanding viral replication and transcription mechanisms is critical for developing effective antiviral strategies. The study of viral gene regulation in host cellular environment is an important bridge for translating mechanistic discoveries from in vitro studies to in vivo but it remains stagnated due to the absence of technological advancement.

Abstract In the current scenario, the available drugs for SARS-CoV-2 are extremely limited. Among the potential therapeutic targets, the RNA-dependent RNA polymerase (RdRp) complex, essential for viral replication and transcription, presents a promising focal point for drug design. This study explores the mechanistic effects of chemically modified nucleoside analogs on the activity of SARS-CoV-2 RdRp and the subsequent chain termination of viral RNA synthesis.