8D36

Crystal structure of SARS-CoV-2 fusion peptide in complex with neutralizing antibody COV44-62

Summary for 8D36

• Entry DOI: 10.2210/pdb8d36/pdb
• Descriptor: Neutralizing antibody COV44-62 heavy chain, Neutralizing antibody COV44-62 light chain, Spike protein S2 fusion peptide, ... (4 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, antibody, fusion peptide, neutralizing antibody, covid-19, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 48689.42

Authors

Yuan, M.,Lee, C.C.D.,Wilson, I.A. (deposition date: 2022-05-31, release date: 2022-07-27, Last modification date: 2023-10-18)

Primary citation

Dacon, C.,Tucker, C.,Peng, L.,Lee, C.D.,Lin, T.H.,Yuan, M.,Cong, Y.,Wang, L.,Purser, L.,Williams, J.K.,Pyo, C.W.,Kosik, I.,Hu, Z.,Zhao, M.,Mohan, D.,Cooper, A.J.R.,Peterson, M.,Skinner, J.,Dixit, S.,Kollins, E.,Huzella, L.,Perry, D.,Byrum, R.,Lembirik, S.,Drawbaugh, D.,Eaton, B.,Zhang, Y.,Yang, E.S.,Chen, M.,Leung, K.,Weinberg, R.S.,Pegu, A.,Geraghty, D.E.,Davidson, E.,Douagi, I.,Moir, S.,Yewdell, J.W.,Schmaljohn, C.,Crompton, P.D.,Holbrook, M.R.,Nemazee, D.,Mascola, J.R.,Wilson, I.A.,Tan, J.
Broadly neutralizing antibodies target the coronavirus fusion peptide.
Science, 377:728-735, 2022

PubMed Abstract: 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.

PubMed: 35857439
DOI: 10.1126/science.abq3773

Experimental method

X-RAY DIFFRACTION (1.45 Å)