{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chan JF"],"funding":["NCI NIH HHS"],"pagination":["eadd3867"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9858505"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(3)"],"pubmed_abstract":["Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry."],"journal":["Science advances"],"pubmed_title":["Altered host protease determinants for SARS-CoV-2 Omicron."],"pmcid":["PMC9858505"],"funding_grant_id":["P30 CA008748"],"pubmed_authors":["Liu H","Cai JP","Yuan S","Chan JF","Yuen TT","Zhang AJ","Shuai H","Hu B","Hou Y","Liu Y","Shi ZL","Yin F","Wen L","Huang X","Yoon C","Zhang BZ","Chu H","Yuen KY","Shi J","Chai Y","Brindley MA","Shi H","Zhu T","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"Altered host protease determinants for SARS-CoV-2 Omicron.","description":"Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-02T11:14:51.113Z","creation":"2025-02-18T23:26:12.806Z"},"accession":"S-EPMC9858505","cross_references":{"pubmed":["36662861"],"doi":["10.1126/sciadv.add3867"]}}