{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Deschenes NM"],"funding":["National Institute of Allergy and Infectious Diseases","Government of Saskatchewan","NIAID NIH HHS","Vancouver General Hospital Foundation","Natural Sciences and Engineering Research Council","National Research Council","Canada Foundation for Innovation","National Institutes of Health","University of Saskatchewan","NIH HHS","Canadian Institutes of Health Research","CIHR"],"pagination":["e789-e798"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12614980"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["232(5)"],"pubmed_abstract":["Background
The main protease (Mpro) is one of the most attractive targets for antiviral drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in Mpro have been linked to resistance against nirmatrelvir-ritonavir (NIR-RIT), an important therapy for SARS-CoV-2 infection. This study aimed to identify low-frequency antiviral resistance mutations in Mpro from NIR-RIT-treated patients and to analyze the enzymatic properties, inhibitor susceptibility, and structural features of new Mpro clinical variants.Methods
We screened 1528 SARS-CoV-2-positive patients from 2 hospitals and identified 17 who remained positive after treatment. Whole-genome sequencing of nasopharyngeal specimens was conducted to identify Mpro clinical variants. The impact"],"journal":["The Journal of infectious diseases"],"pubmed_title":["Functional and Structural Characterization of Treatment-Emergent Nirmatrelvir Resistance Mutations at Low Frequencies in the Main Protease (Mpro) Reveals a Unique Evolutionary Route for SARS-CoV-2 to Gain Resistance."],"pmcid":["PMC12614980"],"funding_grant_id":["R44 AI165188","1R44AI165188-01A1"],"pubmed_authors":["Worrall LJ","Li AX","Lefebvre M","Waglechner N","Maguire F","Farooqi L","Thomas M","Deschenes NM","Strynadka NCJ","Young RN","McGeer A","Malik I","Zhong Z","Siddiqi L","Paetzel M","Kozak RA","Smith JR","Jean F","Moinuddin A","Aftanas P","Cherkasov A","Perez-Vargas J","Mosimann WA","Lim J","Kenward C"],"additional_accession":[]},"is_claimable":false,"name":"Functional and Structural Characterization of Treatment-Emergent Nirmatrelvir Resistance Mutations at Low Frequencies in the Main Protease (Mpro) Reveals a Unique Evolutionary Route for SARS-CoV-2 to Gain Resistance.","description":"Background
The main protease (Mpro) is one of the most attractive targets for antiviral drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in Mpro have been linked to resistance against nirmatrelvir-ritonavir (NIR-RIT), an important therapy for SARS-CoV-2 infection. This study aimed to identify low-frequency antiviral resistance mutations in Mpro from NIR-RIT-treated patients and to analyze the enzymatic properties, inhibitor susceptibility, and structural features of new Mpro clinical variants.Methods
We screened 1528 SARS-CoV-2-positive patients from 2 hospitals and identified 17 who remained positive after treatment. Whole-genome sequencing of nasopharyngeal specimens was conducted to identify Mpro clinical variants. The impact","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-06T13:30:49.954Z","creation":"2026-05-31T03:07:48.661Z"},"accession":"S-EPMC12614980","cross_references":{"pubmed":["40459233"],"doi":["10.1093/infdis/jiaf294"]}}