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In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell\u2013cell fusion assays using SARS-CoV-2-S-transfected 293\u00a0T as effector cells and ACE2-expressing 293\u00a0T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell\u2013cell fusion and virus entry by interfering with the SARS-CoV-2-S\/ACE2 or SARS-CoV-S\/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and\/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.<\/jats:p>","DOI":"10.1038\/s41598-021-84840-3","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T11:03:12Z","timestamp":1615374192000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Blockade of SARS-CoV-2 spike protein-mediated cell\u2013cell fusion using COVID-19 convalescent plasma"],"prefix":"10.1038","volume":"11","author":[{"given":"Ling","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam N. 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