Ni, X.X.NiSchröder, M.M.SchröderOlieric, V.V.OliericSharpe, M.E.M.E.SharpeHernandez-Olmos, V.V.Hernandez-OlmosProschak, E.E.ProschakMerk, D.D.MerkKnapp, S.S.KnappChaikuad, A.A.Chaikuad2022-03-062022-03-062021https://publica.fraunhofer.de/handle/publica/26900410.1021/acsmedchemlett.0c00684The nsP3 macrodomain is a conserved protein interaction module that plays essential regulatory roles in the 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 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, and 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 provide chemical starting points for future inhibitor development.enjournal article