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Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication.
Bravo, Jack P K; Dangerfield, Tyler L; Taylor, David W; Johnson, Kenneth A.
  • Bravo JPK; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
  • Dangerfield TL; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
  • Taylor DW; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA; LIVESTRONG Ca
  • Johnson KA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: kajohnson@utexas.edu.
Mol Cell ; 81(7): 1548-1552.e4, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1051876
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ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / RNA-Dependent RNA Polymerase / RNA, Viral / Adenosine Monophosphate / Alanine / SARS-CoV-2 Limits: Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: J.molcel.2021.01.035

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / RNA-Dependent RNA Polymerase / RNA, Viral / Adenosine Monophosphate / Alanine / SARS-CoV-2 Limits: Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: J.molcel.2021.01.035