tetano
Editor, Senior Moderator
Microbiol Spectr
. 2022 Mar 16;e0181421.
doi: 10.1128/spectrum.01814-21. Online ahead of print.
Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion
Chia-Jung Li[SUP] #[/SUP][SUP] 1 [/SUP], Tai-Ling Chao[SUP] #[/SUP][SUP] 2 3 [/SUP], Ting-Yu Chang[SUP] 1 [/SUP], Chia-Chun Hsiao[SUP] 1 [/SUP], De-Chao Lu[SUP] 1 [/SUP], Yi-Wei Chiang[SUP] 1 [/SUP], Guan-Chun Lai[SUP] 1 [/SUP], Ya-Min Tsai[SUP] 2 [/SUP], Jun-Tung Fang[SUP] 2 [/SUP], Siman Ieong[SUP] 2 [/SUP], Jann-Tay Wang[SUP] 4 [/SUP], Sui-Yuan Chang[SUP] 2 5 [/SUP], Shih-Chung Chang[SUP] 1 6 [/SUP]
Affiliations
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.
Keywords: S2 subunit; SARS-CoV-2; membrane fusion; neutralizing antibodies; spike (S) protein.
. 2022 Mar 16;e0181421.
doi: 10.1128/spectrum.01814-21. Online ahead of print.
Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion
Chia-Jung Li[SUP] #[/SUP][SUP] 1 [/SUP], Tai-Ling Chao[SUP] #[/SUP][SUP] 2 3 [/SUP], Ting-Yu Chang[SUP] 1 [/SUP], Chia-Chun Hsiao[SUP] 1 [/SUP], De-Chao Lu[SUP] 1 [/SUP], Yi-Wei Chiang[SUP] 1 [/SUP], Guan-Chun Lai[SUP] 1 [/SUP], Ya-Min Tsai[SUP] 2 [/SUP], Jun-Tung Fang[SUP] 2 [/SUP], Siman Ieong[SUP] 2 [/SUP], Jann-Tay Wang[SUP] 4 [/SUP], Sui-Yuan Chang[SUP] 2 5 [/SUP], Shih-Chung Chang[SUP] 1 6 [/SUP]
Affiliations
- PMID: 35293796
- DOI: 10.1128/spectrum.01814-21
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.
Keywords: S2 subunit; SARS-CoV-2; membrane fusion; neutralizing antibodies; spike (S) protein.