RT Journal Article
SR Electronic
T1 A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.13.464307
DO 10.1101/2021.10.13.464307
A1 Pengfei Wang
A1 Ryan G. Casner
A1 Manoj S. Nair
A1 Jian Yu
A1 Yicheng Guo
A1 Maple Wang
A1 Jasper F.-W. Chan
A1 Gabriele Cerutti
A1 Sho Iketani
A1 Lihong Liu
A1 Zizhang Sheng
A1 Zhiwei Chen
A1 Kwok-Yung Yuen
A1 Peter D. Kwong
A1 Yaoxing Huang
A1 Lawrence Shapiro
A1 David D. Ho
YR 2021
UL http://biorxiv.org/content/early/2021/10/14/2021.10.13.464307.abstract
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 K378T 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.Competing Interest StatementP.W., J.Y., M.N., Y.H., L.L., and D.D.H. are inventors on a provisional patent application on mAbs to SARS-CoV-2.