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

Emerging Microbes and Infections

Maple Wang¹  David D. Ho¹  Manoj S. Nair¹  Lihong Liu¹  Zizhang Sheng¹  Jian Yu¹  Yaoxing Huang¹  Lawrence Shapiro¹  Yicheng Guo¹  Sho Iketani¹  Pengfei Wang¹  Ryan G. Casner²  Peter D. Kwong²  Gabriele Cerutti²  Jasper F.-W. Chan³  Kwok-Yung Yuen³  Zhiwei Chen³ 

[1] Columbia University Vagelos College of Physicians and Surgeons;Columbia University;Li Ka Shing Faculty of Medicine, The University of Hong Kong;

关键词: sars-cov-2;    antibody;    variants;    sarbecovirus;    sars-cov;   

DOI  :  10.1080/22221751.2021.2011623

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown