Broadly Neutralizing and Protective Nanobodies Against SARS-CoV-2 Omicron Subvariants BA.1, BA.2, and BA.4/5 and Diverse Sarbecoviruses

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Dec 27

PMID 36575191

Authors

Mingxi Li

Yifei Ren

Zhen Qin Aw

Bo Chen

Ziqing Yang

Yuqing Lei

Lin Cheng

Qingtai Liang

Junxian Hong

Yiling Yang

Jing Chen

Yi Hao Wong

Jing Wei

Sisi Shan

Senyan Zhang

Jiwan Ge

Ruoke Wang

Jay Zengjun Dong

Yuxing Chen

Xuanling Shi

Qi Zhang

Zheng Zhang

Justin Jang Hann Chu

Xinquan Wang

Linqi Zhang

Affiliations

Soon will be listed here.

Abstract

As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.

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