{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:50:21Z","timestamp":1787827821935,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TEAM\/2017\u20104\/32"],"award-info":[{"award-number":["TEAM\/2017\u20104\/32"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    The SARS\u2010CoV\u20102 main protease (M\n                    <jats:sup>pro<\/jats:sup>\n                    ) holds significant importance as a biological target in combating coronaviruses due to its importance in virus replication. Considering the emergence of novel SARS\u2010CoV\u20102 variants and the mutations observed in the M\n                    <jats:sup>pro<\/jats:sup>\n                    sequence, we hypothesized that these mutations may have a potential impact on the protease's specificity. To test this, we expressed M\n                    <jats:sup>pro<\/jats:sup>\n                    corresponding to the original strain and variants Beta1, Beta2, and Omicron and analyzed their activity on protein\u2010based and peptide substrates. Although we observed differential activity on the protein\u2010based substrate, there was very little difference when analyzed on the peptide substrate. We conclude that mutations on the M\n                    <jats:sup>pro<\/jats:sup>\n                    sequence, despite having a minor effect on a peptide substrate cleavage, did not change the catalytic site environment enough to build resistance to inhibition. Therefore, we propose that inhibitors initially designed for the M\n                    <jats:sup>pro<\/jats:sup>\n                    of the original strain will be effective in all the variants. Thus, M\n                    <jats:sup>pro<\/jats:sup>\n                    is likely to continue to be a target of therapeutic interest as mutations in its sequence are rare and, as we show here, have a minor effect on the protease's recognition of peptide\u2010based molecules.\n                  <\/jats:p>","DOI":"10.1111\/febs.16970","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T10:29:06Z","timestamp":1697452146000},"page":"61-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential specificity of\n                    <scp>SARS\u2010CoV<\/scp>\n                    \u20102 main protease variants on peptide versus protein\u2010based substrates"],"prefix":"10.1111","volume":"291","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8065-2532","authenticated-orcid":false,"given":"Fernanda R.","family":"Rocho","sequence":"first","affiliation":[{"name":"Cell and Molecular Biology of Cancer Program Sanford Burnham Prebys Medical Discovery Institute  La Jolla CA USA"},{"name":"Medicinal and Biological Chemistry Group of the Department of Chemistry and Molecular Physics University of S\u00e3o Paulo  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Snipas","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology of Cancer Program Sanford Burnham Prebys Medical Discovery Institute  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Shamim","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Group of the Department of Chemistry and Molecular Physics University of S\u00e3o Paulo  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioletta","family":"Rut","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Bioimaging Wroclaw University of Science and Technology  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Drag","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Bioimaging Wroclaw University of Science and Technology  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Montanari","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Group of the Department of Chemistry and Molecular Physics University of S\u00e3o Paulo  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-6732","authenticated-orcid":false,"given":"Guy S.","family":"Salvesen","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology of Cancer Program Sanford Burnham Prebys Medical Discovery Institute  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3405"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2223-y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12936"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.14.6676-6681.2001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb4489"},{"key":"e_1_2_10_7_1","first-page":"178","article-title":"Innate immune evasion strategies of SARS\u2010CoV\u20102","volume":"21","author":"Minkoff JM","year":"2023","journal-title":"Nat Rev 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PeterssonMY ReeseMR SammonsMF TuttleJB VerhoestPR WeiL YangQ&YangX(2021)Nitrile\u2010containing antiviral compounds. WO Patent WO2021\/250648 A1 December 2021."}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.16970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T05:18:58Z","timestamp":1705555138000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.16970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/febs.16970"],"URL":"https:\/\/doi.org\/10.1111\/febs.16970","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/FEBS.16970\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16970\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16970\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16970\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16970\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16970\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]},"assertion":[{"value":"2023-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}