{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T08:50:59Z","timestamp":1781427059453,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["OV3\u2010170644"],"award-info":[{"award-number":["OV3\u2010170644"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u201013694"],"award-info":[{"award-number":["MOP\u201013694"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["327028\u201009"],"award-info":[{"award-number":["327028\u201009"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The 3C\u2010like protease (3CL<jats:sup>pro<\/jats:sup>) is crucial to the replication of SARS\u2010CoV\u20102, the causative agent of COVID\u201019, and is the target of several successful drugs including Paxlovid and Xocova. Nevertheless, the emergence of viral resistance underlines the need for alternative drug strategies. 3CL<jats:sup>pro<\/jats:sup> only functions as a homodimer, making the protein\u2013protein interface an attractive drug target. Dimerization is partly mediated by a conserved glycine at position 11. However, some naturally occurring SARS\u2010CoV\u20102 sequences contain a serine at this position, potentially disrupting the dimer. We have used concentration\u2010dependent activity assays and mass spectrometry to show that indeed the G11S mutation reduces the stability of the dimer by 600\u2010fold. This helps to set a quantitative benchmark for the minimum potency required of any future protein\u2013protein interaction inhibitors targeting 3CL<jats:sup>pro<\/jats:sup> and raises interesting questions regarding how coronaviruses bearing such weakly dimerizing 3CL<jats:sup>pro<\/jats:sup> enzymes are capable of replication.<\/jats:p>","DOI":"10.1002\/pro.4857","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:02:56Z","timestamp":1701993776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A naturally occurring <scp>G11S<\/scp> mutation in the <scp>3C<\/scp>\u2010like protease from the <scp>SARS\u2010CoV<\/scp>\u20102 virus dramatically weakens the dimer interface"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6792-3091","authenticated-orcid":false,"given":"Guanyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe A.","family":"Venegas","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Rueda","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9059-2111","authenticated-orcid":false,"given":"Nuwani W.","family":"Weerasinghe","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5498-344X","authenticated-orcid":false,"given":"Kevin A.","family":"Uggowitzer","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-8362","authenticated-orcid":false,"given":"Christopher J.","family":"Thibodeaux","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-2079","authenticated-orcid":false,"given":"Nicolas","family":"Moitessier","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3767-1225","authenticated-orcid":false,"given":"Anthony K.","family":"Mittermaier","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085658"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-017-0449-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705240200"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvm246"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21519"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.04.027"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13410-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202010316"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2438-7_1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.08.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20220105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2704.203945"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0695-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscombsci.0c00058"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi061746y"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2007.02.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502577200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.3c00538"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05514-2"},{"key":"e_1_2_9_23_1","first-page":"e02815","article-title":"The substitutions l50f, e166a and l167f in sars\u2010cov\u20102 3clpro are selected by a protease inhibitor in vitro and confer resistance to nirmatrelvir","author":"Jochmans D","year":"2023","journal-title":"mBio"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.46234\/ccdcw2021.255"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0262-4079(20)30862-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(06)66005-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00269-12"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01577-x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2744(69)90420-3"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03084-7"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4784"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2007.03.012"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.114046"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19424-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.651463"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00117"},{"key":"e_1_2_9_37_1","article-title":"Rational design of peptide\u2010based inhibitors disrupting protein\u2010protein interactions","volume":"9","author":"Wang X","year":"2021","journal-title":"Front Chem"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.1c00085"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.11.102"},{"key":"e_1_2_9_40_1","unstructured":"World Health Organization.Coronavirus disease (Covid\u201019) pandemic (accessed July 10 2023).2023.https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019."},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.11.073"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100280RR"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-021-00853-0"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3405"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-010-0044-8"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add7197"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-4-853"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.4857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T13:36:22Z","timestamp":1704980182000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.4857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/pro.4857"],"URL":"https:\/\/doi.org\/10.1002\/pro.4857","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"assertion":[{"value":"2023-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4857"}}