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An Update on the Current State of SARS-CoV-2 Mac1 Inhibitors

7 Oct 2023

Abstract excerpt

Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that promotes replication and blocks IFN responses, though the precise mechanisms it uses to carry out these functions remain...

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PMID: 37887737
DOI: 10.3390/pathogens12101221

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An Update on the Current State of SARS-CoV-2 Mac1 InhibitorsPMID 37887737Read ↗

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2Semantic proximity Read ↗

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2Semantic proximity Read ↗

Identification of a series of pyrrolo-pyrimidine-based SARS-CoV-2 Mac1 inhibitors that repress coronavirus replicationSemantic proximity Read ↗

Identification of a series of pyrrolo-pyrimidine based SARS-CoV-2 Mac1 inhibitors that repress coronavirus replicationSemantic proximity Read ↗

The SARS-CoV-2 Conserved Macrodomain Is a Mono-ADP-RibosylhydrolaseSemantic proximity Read ↗

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in miceSemantic proximity Read ↗

Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral targetSemantic proximity Read ↗

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in miceSemantic proximity Read ↗

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis <i>in vivo</i>Semantic proximity Read ↗

An MHV macrodomain mutant predicted to lack ADP-ribose binding activity is severely attenuated, indicating multiple roles for the macrodomain in coronavirus replicationSemantic proximity Read ↗

Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational DockingSemantic proximity Read ↗

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivoSemantic proximity Read ↗

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