Structural insights into plasticity and discovery of remdesivir metabolite GS-441524 binding in SARS-CoV-2 macrodomain

  • The nsP3 macrodomain is a conserved protein interaction module that plays essential regulatory roles in host immune response by recognizing and removing posttranslational ADP-ribosylation sites during SARS-CoV-2 infection. Thus, targeting this protein domain may offer a therapeutic strategy to combat the current and future virus pandemics. To assist inhibitor development efforts, we report here a comprehensive set of macrodomain crystal structures complexed with diverse naturally-occurring nucleotides, small molecules as well as nucleotide analogues including GS-441524 and its phosphorylated analogue, active metabolites of remdesivir. The presented data strengthen our understanding of the SARS-CoV-2 macrodomain structural plasticity and it provides chemical starting points for future inhibitor development.

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Author:Xiaomin NiORCiDGND, Martin SchröderORCiDGND, Vincent OliericORCiDGND, May E. Sharpe, Hernandez-Olmos OlmosORCiD, Ewgenij ProschakORCiDGND, Daniel MerkORCiDGND, Stefan KnappORCiD, Apirat ChaikuadORCiD
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2021/03/04
Date of first Publication:2021/03/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/08/06
Page Number:12
Institutes:Biochemie, Chemie und Pharmazie
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International