Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion

• DOI: 10.1128/spectrum.01814-21
• Publication Date: 2022-03-16T13:00:42Z
• Authors: Chia-Jung Li; Tai-Ling Chao; Ting-Yu Chang; Chia-Chun Hsiao; De-Chao Lu; Yi-Wei Chiang; Guan-Chun Lai; Ya-Min Tsai; Jun-Tung Fang; Siman Ieong; Jann-Tay Wang; Sui-Yuan Chang; Shih-Chung Chang
• Keywords: 0301 basic medicine; SARS-CoV-2; Immune Sera; membrane fusion; Antibodies, Monoclonal; COVID-19; Antibodies, Viral; Microbiology; Antibodies, Neutralizing; Membrane Fusion; QR1-502; 3. Good health; S2 subunit; Epitopes; Mice; 03 medical and health sciences; Spike Glycoprotein, Coronavirus; Animals; neutralizing antibodies; spike (S) protein; Research Article

Most of SARS-CoV-2 neutralizing antibodies (nAbs) targeted the receptor binding domain (RBD) spike (S) protein. However, mutations at RBD sequences found in emerging variants greatly reduced effectiveness nAbs. Here we showed that four nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, which recognized a conserved epitope S2 subunit S protein, can inhibit infection through blocking protein-mediated membrane fusion. Notably, these nAbs exhibited broadly activity against Alpha, Gamma, Delta, Epsilon variants. Antisera collected from mice immunized with identified peptides also potent virus activity. Discovery S2-specific their unique antigenic epitopes paves new path for development COVID-19 therapeutics vaccines. IMPORTANCE The protein on surface mediates virus-host cell fusion during entry. Many (nAbs), lost newly sequence RBD. In contrast, nAb highly subunit, plays key role fusion, was poorly discovered. We inhibited These induced by possessed This work not only unveiled but discovered an immunodominant be rationally designed as broad-spectrum vaccine SARS-like coronaviruses.