{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:42:33Z","timestamp":1790656953263,"version":"4.1.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012632","name":"Nazarbayev University","doi-asserted-by":"publisher","award":["280720FD1907"],"award-info":[{"award-number":["280720FD1907"]}],"id":[{"id":"10.13039\/501100012632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The serine proteases neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and neutrophil serine protease 4 (NSP4) are secreted by activated neutrophils as a part of the innate immune response against invading pathogens. However, these serine proteases might be adopted by viruses to mediate viral surface protein priming resulting in host cell entrance and productive infection. Indeed, NE and PR3 hydrolyze the scissile peptide bond within the proteolytically sensitive polybasic sequence of the activation loop of SARS-CoV-2 located at the S1\/S2 interface of the Spike (S) protein; an amino acid motif which differs from SARS-CoV-1. The occurrence of novel SARS-CoV-2 variants and substitution of distinct amino acids at the polybasic sequence prompts serious concerns regarding increased transmissibility. We propose that a novel cleavage site by CatG of the Omicron variant and the increased substrate turnover of the Delta variant by furin within the polybasic sequence should be considered for increased transmission of SARS-CoV-2 variants.<\/jats:p>","DOI":"10.1371\/journal.pone.0264723","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T17:33:50Z","timestamp":1650303230000},"page":"e0264723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Occurrence of a novel cleavage site for cathepsin G adjacent to the polybasic sequence within the proteolytically sensitive activation loop of the SARS-CoV-2 Omicron variant: The amino acid substitution N679K and P681H of the spike protein"],"prefix":"10.1371","volume":"17","author":[{"given":"Zhadyra","family":"Mustafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Kalbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-6558","authenticated-orcid":true,"given":"Timo","family":"Burster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"pone.0264723.ref001","doi-asserted-by":"crossref","first-page":"105778","DOI":"10.1016\/j.actatropica.2020.105778","article-title":"One year update on the COVID-19 pandemic: Where are we now?","volume":"214","author":"SK Mishra","year":"2021","journal-title":"Acta Trop"},{"issue":"7798","key":"pone.0264723.ref002","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"P Zhou","year":"2020","journal-title":"Nature"},{"issue":"2","key":"pone.0264723.ref003","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.","volume":"181","author":"AC Walls","year":"2020","journal-title":"Cell"},{"issue":"9","key":"pone.0264723.ref004","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202000786","article-title":"TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells","volume":"3","author":"D Bestle","year":"2020","journal-title":"Life Sci Alliance"},{"key":"pone.0264723.ref005","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.64508","article-title":"SARS-CoV-2 entry into human airway organoids is serine protease-mediated and facilitated by the multibasic cleavage site","volume":"10","author":"AZ Mykytyn","year":"2021","journal-title":"Elife"},{"issue":"35","key":"pone.0264723.ref006","doi-asserted-by":"crossref","first-page":"12543","DOI":"10.1073\/pnas.0503203102","article-title":"Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection","volume":"102","author":"S Matsuyama","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0264723.ref007","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1016\/j.jinf.2020.12.024","article-title":"Emergence of a new SARS-CoV-2 variant in the UK.","volume":"82","author":"JW Tang","year":"2021","journal-title":"J Infect"},{"key":"pone.0264723.ref008","article-title":"SARS-CoV-2 variants of concern are emerging in India","author":"J Singh","year":"2021","journal-title":"Nat Med"},{"key":"pone.0264723.ref009","article-title":"Estimating the strength of selection for new SARS-CoV-2 variants.","author":"CH van Dorp","year":"2021","journal-title":"medRxiv"},{"issue":"7865","key":"pone.0264723.ref010","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/d41586-021-01696-3","article-title":"Delta coronavirus variant: scientists brace for impact","volume":"595","author":"E. 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