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Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion.
Li, Chia-Jung; Chao, Tai-Ling; Chang, Ting-Yu; Hsiao, Chia-Chun; Lu, De-Chao; Chiang, Yi-Wei; Lai, Guan-Chun; Tsai, Ya-Min; Fang, Jun-Tung; Ieong, Siman; Wang, Jann-Tay; Chang, Sui-Yuan; Chang, Shih-Chung.
  • Li CJ; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Chao TL; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Chang TY; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsiao CC; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Lu DC; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Chiang YW; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Lai GC; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Tsai YM; Department of Biochemical Science and Technology, College of Life Science, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Fang JT; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Ieong S; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Wang JT; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
  • Chang SY; Department of Internal Medicine, National Taiwan Universitygrid.19188.39 Hospital, Taipei, Taiwan.
  • Chang SC; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan Universitygrid.19188.39, Taipei, Taiwan.
Microbiol Spectr ; 10(2): e0181421, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1745800
ABSTRACT
Most 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. IMPORTANCE The spike (S) protein on the surface of SARS-CoV-2 mediates receptor binding and virus-host cell membrane fusion during virus entry. Many neutralizing antibodies (nAbs), which targeted the receptor binding domain (RBD) of S protein, lost the neutralizing activity against the newly emerging SARS-CoV-2 variants with sequence mutations at the RBD. In contrast, the nAb against the highly conserved S2 subunit, which plays the key role in virus-host cell membrane fusion, was poorly discovered. We showed that four S2-specific nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, inhibited SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. These nAbs exhibited broadly neutralizing activity against Alpha, Gamma, Delta, and Epsilon variants. Antisera induced by the identified epitope peptides also possessed potent neutralizing activity. This work not only unveiled the S2-specific nAbs but also discovered an immunodominant epitope in the S2 subunit that can be rationally designed as the broad-spectrum vaccine against the SARS-like coronaviruses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01814-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01814-21