{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Pfannenstiel JJ"],"funding":["NCATS NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["Coronaviruses (CoVs) can emerge from zoonotic sources and cause severe diseases in humans and animals. All CoVs encode for a macrodomain (Mac1) that binds to and removes ADP-ribose from target proteins. SARS-CoV-2 Mac1 promotes virus replication in the presence of interferon (IFN) and blocks the production of IFN, though the mechanisms by which it mediates these functions remain unknown. Mac1 inhibitors could help elucidate these mechanisms and serve as therapeutic agents against CoV-induced diseases. We previously identified compound <b>4a</b> (a.k.a. MCD-628), a pyrrolo-pyrimidine that inhibited Mac1 activity <i>in vitro</i> at low micromolar levels. Here, we determined the binding mode of <b>4a</b> by crystallography, further defining its interaction with Mac1. However, <b>4a</b> did no"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.10.28.620664"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11565749"],"repository":["biostudies-literature"],"pubmed_title":["Identification of a series of pyrrolo-pyrimidine based SARS-CoV-2 Mac1 inhibitors that repress coronavirus replication."],"pmcid":["PMC11565749"],"funding_grant_id":["P20 GM113117","R35 GM138029","UL1 TR002366"],"pubmed_authors":["O'Connor J","Duong MTH","Roy A","Lehtio L","Sherrill LM","Cadoux G","Saenjamsai P","Pfannenstiel JJ","Feng M","Fehr AR","Colquhoun I","Hageman MJ","Johnson DK","Paakkonen J","Ferraris DV","Thorne D","Schemmel NF","Cluff D"],"additional_accession":[]},"is_claimable":false,"name":"Identification of a series of pyrrolo-pyrimidine based SARS-CoV-2 Mac1 inhibitors that repress coronavirus replication.","description":"Coronaviruses (CoVs) can emerge from zoonotic sources and cause severe diseases in humans and animals. All CoVs encode for a macrodomain (Mac1) that binds to and removes ADP-ribose from target proteins. SARS-CoV-2 Mac1 promotes virus replication in the presence of interferon (IFN) and blocks the production of IFN, though the mechanisms by which it mediates these functions remain unknown. Mac1 inhibitors could help elucidate these mechanisms and serve as therapeutic agents against CoV-induced diseases. We previously identified compound <b>4a</b> (a.k.a. MCD-628), a pyrrolo-pyrimidine that inhibited Mac1 activity <i>in vitro</i> at low micromolar levels. Here, we determined the binding mode of <b>4a</b> by crystallography, further defining its interaction with Mac1. However, <b>4a</b> did no","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-04-25T03:28:30.436Z","creation":"2025-04-06T10:12:25.108Z"},"accession":"S-EPMC11565749","cross_references":{"pubmed":["39554145"],"doi":["10.1101/2024.10.28.620664"]}}