Nature communications · 2022
Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Li Mingxi, Ren Yifei, Aw Zhen Qin, Chen Bo, Yang Ziqing, Lei Yuqing, Cheng Lin, Liang Qingtai, Hong Junxian, Yang Yiling, Chen Jing, Wong Yi Hao, Wei Jing, Shan Sisi, Zhang Senyan, Ge Jiwan, Wang Ruoke, Dong Jay Zengjun, Chen Yuxing, Shi Xuanling, Zhang Qi, Zhang Zheng, Chu Justin Jang Hann, Wang Xinquan, Zhang Linqi
Аннотация
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.