A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses

Pengfei Wang; Ryan G. Casner; Manoj S. Nair; Jian Yu; Yicheng Guo; Maple Wang; Jasper F.W. Chan; Gabriele Cerutti; Sho Iketani; Lihong Liu; Zizhang Sheng; Zhiwei Chen; Kwok Yung Yuen; Peter D. Kwong; Yaoxing Huang; Lawrence Shapiro; David D. Ho

doi:10.1080/22221751.2021.2011623

A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses

Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Jian Yu, Yicheng Guo, Maple Wang, Jasper F.W. Chan, Gabriele Cerutti, Sho Iketani, Lihong Liu, Zizhang Sheng, Zhiwei Chen, Kwok Yung Yuen, Peter D. Kwong, Yaoxing Huang, Lawrence Shapiro, David D. Ho

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2–36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2–36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2–36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

Original language	English
Pages (from-to)	147-157
Number of pages	11
Journal	Emerging Microbes and Infections
Volume	11
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2021.2011623
Publication status	Published - 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

ASJC Scopus Subject Areas

Epidemiology
Parasitology
Microbiology
Immunology
Drug Discovery
Infectious Diseases
Virology

Keywords

SARS-CoV
SARS-CoV-2
antibody
sarbecovirus
variants

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10.1080/22221751.2021.2011623

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Wang, P., Casner, R. G., Nair, M. S., Yu, J., Guo, Y., Wang, M., Chan, J. F. W., Cerutti, G., Iketani, S., Liu, L., Sheng, Z., Chen, Z., Yuen, K. Y., Kwong, P. D., Huang, Y., Shapiro, L., & Ho, D. D. (2022). A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. Emerging Microbes and Infections, 11(1), 147-157. https://doi.org/10.1080/22221751.2021.2011623

Wang, P, Casner, RG, Nair, MS, Yu, J, Guo, Y, Wang, M, Chan, JFW, Cerutti, G, Iketani, S, Liu, L, Sheng, Z, Chen, Z, Yuen, KY, Kwong, PD, Huang, Y, Shapiro, L & Ho, DD 2022, 'A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses', Emerging Microbes and Infections, vol. 11, no. 1, pp. 147-157. https://doi.org/10.1080/22221751.2021.2011623

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AB - The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2–36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2–36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2–36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

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A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

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