Rapid resistance profiling of SARS-CoV-2 protease inhibitors

DOI record: { "DOI": "10.1038/s44259-023-00009-0", "ISSN": [ "2731-8745" ], "URL": "http://dx.doi.org/10.1038/s44259-023-00009-0", "abstract": "<jats:title>Abstract</jats:title><jats:p>Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M<jats:sup>pro</jats:sup>) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and <jats:italic>vice versa</jats:italic>.</jats:p>", "alternative-id": [ "9" ], "article-number": "9", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "25 February 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "23 June 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "20 August 2023" }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 1, "value": "The M^pro gain-of-signal system is the subject of U.S. Provisional Application Serial No. 63/108,611, filed on November 2, 2020, with R.S.H. and S.A.M. as inventors. The authors declare no additional competing interests." }, { "group": { "label": "Ethics", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "Studies here were performed under University of Minnesota IBC protocol 1902-36822H to R.S.H., University of Minnesota IBC protocol 2111-39591H to D.A.H., and University of Texas Health. San Antonio IBC B-00000013853 to R.S.H." } ], "author": [ { "affiliation": [], "family": "Moghadasi", "given": "Seyed Arad", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-9656-9175", "affiliation": [], "authenticated-orcid": false, "family": "Biswas", "given": "Rayhan G.", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5950-931X", "affiliation": [], "authenticated-orcid": false, "family": "Harki", "given": "Daniel A.", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-9034-9112", "affiliation": [], "authenticated-orcid": false, "family": "Harris", "given": "Reuben S.", "sequence": "additional" } ], "container-title": "npj Antimicrobials and Resistance", "container-title-short": "npj Antimicrob Resist", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2023, 8, 20 ] ], "date-time": "2023-08-20T22:01:44Z", "timestamp": 1692568904000 }, "deposited": { "date-parts": [ [ 2023, 8, 20 ] ], "date-time": "2023-08-20T22:01:46Z", "timestamp": 1692568906000 }, "funder": [ { "DOI": "10.13039/100000060", "award": [ "U19-AI171954" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100000060", "id-type": "DOI" } ], "name": "U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases" } ], "indexed": { "date-parts": [ [ 2024, 9, 14 ] ], "date-time": "2024-09-14T15:13:36Z", "timestamp": 1726326816818 }, "is-referenced-by-count": 18, "issue": "1", "issued": { "date-parts": [ [ 2023, 8, 20 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2023, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 8, 20 ] ], "date-time": "2023-08-20T00:00:00Z", "timestamp": 1692489600000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 8, 20 ] ], "date-time": "2023-08-20T00:00:00Z", "timestamp": 1692489600000 } } ], "link": [ { "URL": "https://www.nature.com/articles/s44259-023-00009-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s44259-023-00009-0", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s44259-023-00009-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1038", "published": { "date-parts": [ [ 2023, 8, 20 ] ] }, "published-online": { "date-parts": [ [ 2023, 8, 20 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1016/j.mam.2022.101159", "author": "T Majerova", "doi-asserted-by": "publisher", "first-page": "101159", "journal-title": "Mol. 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