Li, Chia JungChia JungLiTAI-LING CHAOChang, Ting YuTing YuChangHsiao, Chia ChunChia ChunHsiaoLu, De ChaoDe ChaoLuChiang, Yi WeiYi WeiChiangLai, Guan ChunGuan ChunLaiTsai, Ya MinYa MinTsaiFang, Jun TungJun TungFangIeong, SimanSimanIeongJANN-TAY WANGSUI-YUAN CHANGSHIH-CHUNG CHANG2022-05-142022-05-142022-04-0121650497https://scholars.lib.ntu.edu.tw/handle/123456789/610993Most of SARS-CoV-2 neutralizing antibodies (nAbs) targeted the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, mutations at RBD sequences found in the emerging SARS-CoV-2 variants greatly reduced the effectiveness of nAbs. Here we showed that four nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, which recognized a conserved epitope in the S2 subunit of the S protein, can inhibit SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. Notably, these four nAbs exhibited broadly neutralizing activity against SARS-CoV-2 Alpha, Gamma, Delta, and Epsilon variants. Antisera collected from mice immunized with the identified epitope peptides of these four nAbs also exhibited potent virus neutralizing activity. Discovery of the S2-specific nAbs and their unique antigenic epitopes paves a new path for development of COVID-19 therapeutics and vaccines.membrane fusion | neutralizing antibodies | S2 subunit | SARS-CoV-2 | spike (S) protein[SDGs]SDG3journal article10.1128/spectrum.01814-21352937962-s2.0-85129262625https://api.elsevier.com/content/abstract/scopus_id/85129262625