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A broad and potent neutralization epitope in SARS-related coronaviruses
Meng Yuan; Xueyong Zhu; Wan-ting He; Panpan Zhou; Chengzi I Kaku; Tazio Capozzola; Connie Y Zhu; Xinye Yu; Hejun Liu; Wenli Yu; Yuanzi Hua; Henry Tien; Linghang Peng; Ge Song; Christopher Cottrell; William R Schief; David Nemazee; Laura M Walker; Raiees Andrabi; Dennis Burton; Ian A Wilson.
Affiliation
  • Meng Yuan; The Scripps Research Institute
  • Xueyong Zhu; The Scripps Research Institute
  • Wan-ting He; The Scripps Research Institute
  • Panpan Zhou; The Scripps Research Institute
  • Chengzi I Kaku; Adimab, LLC
  • Tazio Capozzola; The Scripps Research Institute
  • Connie Y Zhu; The Scripps Research Institute
  • Xinye Yu; The Scripps Research Institute
  • Hejun Liu; The Scripps Research Institute
  • Wenli Yu; The Scripps Research Institute
  • Yuanzi Hua; The Scripps Research Institute
  • Henry Tien; The Scripps Research Institute
  • Linghang Peng; The Scripps Research Institute
  • Ge Song; The Scripps Research Institute
  • Christopher Cottrell; The Scripps Reaserch Institutte
  • William R Schief; The Scripps Research Institute
  • David Nemazee; The Scripps Research Institute
  • Laura M Walker; Adimab
  • Raiees Andrabi; The Scripps Research Institute
  • Dennis Burton; Scripps Institute
  • Ian A Wilson; The Scripps Research Institute
Preprint in English | bioRxiv | ID: ppbiorxiv-484037
ABSTRACT
Many neutralizing antibodies (nAbs) elicited to ancestral SARS-CoV-2 through natural infection and vaccination generally have reduced effectiveness to SARS-CoV-2 variants. Here we show therapeutic antibody ADG20 is able to neutralize all SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize all VOCs, albeit with reduced potency against Omicron. Thus, this highly conserved and vulnerable site can be exploited for design of universal vaccines and therapeutic antibodies.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
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