7LQ7

Crystal structure of SARS-CoV-2 receptor binding domain in complex with antibodies CV503 and COVA1-16

Summary for 7LQ7

• Entry DOI: 10.2210/pdb7lq7/pdb
• Descriptor: Spike protein S1, CV503 heavy chain, CV503 light chain, ... (6 entities in total)
• Functional Keywords: antibody, coronavirus, fab, spike, covid-19, rbd, receptor binding domain, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 15
• Total formula weight: 354301.03

Authors

Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2021-02-13, release date: 2021-09-15, Last modification date: 2024-10-23)

Primary citation

Cho, H.,Gonzales-Wartz, K.K.,Huang, D.,Yuan, M.,Peterson, M.,Liang, J.,Beutler, N.,Torres, J.L.,Cong, Y.,Postnikova, E.,Bangaru, S.,Talana, C.A.,Shi, W.,Yang, E.S.,Zhang, Y.,Leung, K.,Wang, L.,Peng, L.,Skinner, J.,Li, S.,Wu, N.C.,Liu, H.,Dacon, C.,Moyer, T.,Cohen, M.,Zhao, M.,Lee, F.E.,Weinberg, R.S.,Douagi, I.,Gross, R.,Schmaljohn, C.,Pegu, A.,Mascola, J.R.,Holbrook, M.,Nemazee, D.,Rogers, T.F.,Ward, A.B.,Wilson, I.A.,Crompton, P.D.,Tan, J.
Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern.
Sci Transl Med, 13:eabj5413-eabj5413, 2021

PubMed Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of existing vaccines and therapeutic antibodies and underscores the need for additional antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells collected from patients with coronavirus disease 2019. The three most potent antibodies targeted distinct regions of the receptor binding domain (RBD), and all three neutralized the SARS-CoV-2 Alpha and Beta variants. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the angiotensin-converting enzyme 2 receptor, and has limited contact with key variant residues K417, E484, and N501. We designed bispecific antibodies by combining nonoverlapping specificities and identified five bispecific antibodies that inhibit SARS-CoV-2 infection at concentrations of less than 1 ng/ml. Through a distinct mode of action, three bispecific antibodies cross-linked adjacent spike proteins using dual N-terminal domain–RBD specificities. One bispecific antibody was greater than 100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a dose of 2.5 mg/kg. Two bispecific antibodies in our panel comparably neutralized the Alpha, Beta, Gamma, and Delta variants and wild-type virus. Furthermore, a bispecific antibody that neutralized the Beta variant protected hamsters against SARS-CoV-2 expressing the E484K mutation. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.

PubMed: 34519517
DOI: 10.1126/scitranslmed.abj5413

Experimental method

X-RAY DIFFRACTION (3.4 Å)