Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication

Remdesivir is a nucleoside analog approved by the US FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryo-EM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of 3 copies of remdesivir monophosphate (RMP) and a partially inco...

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Detalles Bibliográficos
Autores principales: Bravo, Jack P.K., Dangerfield, Tyler L., Taylor, David W., Johnson, Kenneth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2021
Materias:
Short Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843106/
https://www.ncbi.nlm.nih.gov/pubmed/33631104
http://dx.doi.org/10.1016/j.molcel.2021.01.035
Descripción
Sumario:Remdesivir is a nucleoside analog approved by the US FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryo-EM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of 3 copies of remdesivir monophosphate (RMP) and a partially incorporated fourth RMP in the active site. The structure reveals that RMP blocks RNA translocation after incorporation of 3 bases following RMP, resulting in delayed chain termination, which can guide the rational design of improved antiviral drugs.

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