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
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author Bravo, Jack P.K.
Dangerfield, Tyler L.
Taylor, David W.
Johnson, Kenneth A.
author_facet Bravo, Jack P.K.
Dangerfield, Tyler L.
Taylor, David W.
Johnson, Kenneth A.
author_sort Bravo, Jack P.K.
collection PubMed
description 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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spelling pubmed-78431062021-01-29 Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication Bravo, Jack P.K. Dangerfield, Tyler L. Taylor, David W. Johnson, Kenneth A. Mol Cell Short Article 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. Elsevier Inc. 2021-04-01 2021-01-28 /pmc/articles/PMC7843106/ /pubmed/33631104 http://dx.doi.org/10.1016/j.molcel.2021.01.035 Text en © 2021 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Short Article
Bravo, Jack P.K.
Dangerfield, Tyler L.
Taylor, David W.
Johnson, Kenneth A.
Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title_full Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title_fullStr Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title_full_unstemmed Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title_short Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication
title_sort remdesivir is a delayed translocation inhibitor of sars-cov-2 replication
topic Short Article
url 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
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