Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses

Li, Mingxi1; Ren, Yifei2,3; Aw, Zhen Qin4,5,6; Chen, Bo7; Yang, Ziqing1; Lei, Yuqing1; Cheng, Lin8,9; Liang, Qingtai1; Hong, Junxian1; Yang, Yiling1; Chen, Jing2,3; Wong, Yi Hao4,5,6; Wei, Jing1; Shan, Sisi1; Zhang, Senyan2; Ge, Jiwan2,3; Wang, Ruoke1; Dong, Jay Zengjun10; Chen, Yuxing11; Shi, Xuanling1; Zhang, Qi1; Zhang, Zheng8,9; Chu, Justin Jang Hann4,5,6,12; Wang, Xinquan2; Zhang, Linqi1,13,14

2022-12-27

10.1038/s41467-022-35642-2

NATURE COMMUNICATIONS   Impact Factor & Quartile

2041-1723

["The authors identify nanobodies from immunized alpaca with broadly neutralizing activity against SARS-CoV-1, SARS-CoV-2 variants, and major sarbecoviruses. One representative nanobody binds to a highly conserved epitope on RBD and protects K18-hACE2 mice from Omicron and Delta infection.","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."]

SCI

English

Others

National Key Plan for Scientific Research and Development of China["2021YFC0864500","2022YFC2604103","2022YFC2303403","2022YFF1203100","2021YFC2300104"] ; National Natural Science Foundation["92169205","82150205","32270983","32171202"] ; Wanke Scientific Research Program[20221080056] ; Singapore National Medical Research Council Centre Grant Program["CGAug16M009","NUHSRO/2020/066/NUSMedCovid/01/BSL3","NUHSRO/2020/050/ RO5?+?5/NUHS-COVID/4"] ; Singapore Ministry of Health[MOH-COVID19RF2-0001]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000935585400008

NATURE PORTFOLIO

Web of Science

1.Tsinghua Univ, Ctr Global Hlth & Infect Dis, Comprehens AIDS Res Ctr, NexVac Res Ctr,Dept Basic Med Sci,Sch Med, Beijing 100084, Peoples R China
2.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Beijing Frontier Res Ctr Biol Struct, Collaborat Innovat Ctr Biotherapy,Minist Educ,Key, Beijing 100084, Peoples R China
3.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
4.Natl Univ Singapore, Yong Loo Lin Sch Med, Biosafety Level 3 Core Facil, Singapore 119077, Singapore
5.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Lab Mol RNA Virol & Antiviral Strategies, Singapore 119077, Singapore
6.Natl Univ Singapore, Yong Loo Lin Sch Med, Infect Dis Translat Res Programme, Singapore 119077, Singapore
7.NB BIOLAB Co Ltd, Chengdu 611137, Peoples R China
8.Shenzhen Third Peoples Hosp, Inst Hepatol, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China
9.Southern Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen 518112, Peoples R China
10.HplanetBio Co Ltd, Shanghai 200131, Peoples R China
11.Hua Bio Co, Ltd, Hangzhou 310018, Peoples R China
12.Agcy Sci Technol & Res, Inst Mol & Cell Biol, Collaborat & Translat Unit HFMD, Singapore 138673, Singapore
13.Tsinghua Univ, Inst Biopharmaceut & Hlth Engn, Tsinghua Shenzhen Int Grad Sch, Shenzhen 518055, Peoples R China
14.Inst Biomed Hlth Technol & Engn, Shenzhen Bay Lab, Shenzhen 518132, Peoples R China

Li, Mingxi,Ren, Yifei,Aw, Zhen Qin,et al. Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses[J]. NATURE COMMUNICATIONS,2022,13(1).

Li, Mingxi.,Ren, Yifei.,Aw, Zhen Qin.,Chen, Bo.,Yang, Ziqing.,...&Zhang, Linqi.(2022).Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.NATURE COMMUNICATIONS,13(1).

Li, Mingxi,et al."Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses".NATURE COMMUNICATIONS 13.1(2022).