作者: Yang, Eun Sung ; Skinner, Jeff ; Lin, Ting-Hui ; Cong, Yu ; Weinberg, Rona S. ; Crompton, Peter D. ; Hu, Zhe ; Perry, Donna ; Cooper, Andrew J. R. ; Mascola, John R. ; Schmaljohn, Connie ; Douagi, Iyadh ; Wilson, Ian A. ; Byrum, Russell ; Pyo, Chul-Woo ; Peng, Linghang ; Tucker, Courtney ; Drawbaugh, David ; Leung, Kwanyee ; Nemazee, David ; Geraghty, Daniel E. ; Davidson, Edgar ; Zhang, Yi ; Pegu, Amarendra ; Kollins, Erin ; Moir, Susan ; Zhao, Ming ; Wang, Lingshu ; Huzella, Louis ; Purser, Lauren ; Tan, Joshua ; Lembirik, Sanae ; Dacon, Cherrelle ; Yewdell, Jonathan W. ; Mohan, Divya ; Williams, Jazmean K. ; Lee, Chang-Chun D. ; Kosik, Ivan ; Holbrook, Michael R. ; Peterson, Mary ; Chen, Man ; Yuan, Meng ; Eaton, Brett ; Dixit, Saurabh

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2′ cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain–specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2′ cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

Broadly neutralizing antibodies target the coronavirus fusion peptide

作者: Nemazee, David ; Lembirik, Sanae ; Moir, Susan ; Geraghty, Daniel E ; Dixit, Saurabh ; Wang, Lingshu ; Weinberg, Rona S ; Pegu, Amarendra ; Williams, Jazmean K ; Tan, Joshua ; Peterson, Mary ; Yewdell, Jonathan W ; Byrum, Russell ; Kosik, Ivan ; Zhao, Ming ; Hu, Zhe ; Holbrook, Michael R ; Yuan, Meng ; Leung, Kwanyee ; Kollins, Erin ; Schmaljohn, Connie ; Wilson, Ian A ; Davidson, Edgar ; Peng, Linghang ; Pyo, Chul-Woo ; Purser, Lauren ; Zhang, Yi ; Huzella, Louis ; Douagi, Iyadh ; Dacon, Cherrelle ; Mohan, Divya ; Skinner, Jeff ; Crompton, Peter D ; Chen, Man ; Cooper, Andrew ; Cong, Yu ; Yang, Eun Sung ; Lee, Chang-Chun D ; Lin, Ting-Hui ; Mascola, John R ; Tucker, Courtney ; Perry, Donna

AbstractThe potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2’ cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2’ cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.One-Sentence SummaryRare monoclonal antibodies from COVID-19 convalescent individuals broadly neutralize coronaviruses by targeting the fusion peptide.

100 项与 COV44-79 相关的药物交易

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