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Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane\u2010fusion kinetics on human lung\u2010derived cells (Calu\u20103). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccine sera against XBB infection. We found that the sera from elderly convalescent patients who experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2\u2010 or BA.5\u2010infected elderly. On the other hand, we found that the pan\u2010CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB\u2010S\u2010 or XBB.1.5\u2010S\u2010mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2\u2010 or BA.5\u2010infected patients against XBB and XBB.1.5 infection, further indicating that EK1\u2010based pan\u2010CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants.<\/jats:p>","DOI":"10.1002\/jmv.28641","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T04:49:35Z","timestamp":1678337375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["SARS\u2010CoV\u20102 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan\u2010coronavirus fusion inhibitors"],"prefix":"10.1002","volume":"95","author":[{"given":"Shuai","family":"Xia","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology 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