Hetero-bivalent nanobodies provide broad-spectrum protection against SARS-CoV-2 variants of concern including Omicron  

作　　者：Huan Ma Xinghai Zhang Peiyi Zheng Peter H.Dube Weihong Zeng Shaohong Chen Qingyu Cheng Yunru Yang Yan Wu Junhui Zhou Xiaowen Hu Yan Xiang Huajun Zhang Sandra Chiu Tengchuan Jin 

机构地区：[1]Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of USTC Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui,China [2]State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Meg-cience,Chinese Academy of Sciences,Wuhan,Hubei,China [3]Laboratory of Structural Immunology,CAS Key Laboratory of Innate Immunity and Chronic Disease,Hefei National Laboratory for Physical Sciences at Microscale,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui,China [4]Department of Microbiology,Immunology and Molecular Genetics,University of Texas Health Science Center at San Antonio,San Antonio,TX,USA [5]University of Chinese Academy of Sciences,Beijing,China [6]Institute of Health and Medicine,Hefei Comprehensive National Science Center,Hefei,Anhui,China

出　　处：《Cell Research》2022年第9期831-842,共12页细胞研究（英文版）

摘　　要：SARS-CoV-2 variants with adaptive mutations have continued to emerge,causing fresh waves of infection even amongst vaccinated population.The development of broad-spectrum antivirals is thus urgently needed.We previously developed two hetero-bivalent nanobodies(Nbs),aRBD-2-5 and aRBD-2-7,with potent neutralization activity against the wild-type(WT)Wuhan isolated SARS-CoV-2,by fusing aRBD-2 with aRBD-5 and aRBD-7,respectively.Here,we resolved the crystal structures of these Nbs in complex with the receptor-binding domain(RBD)of the spike protein,and found that aRBD-2 contacts with highly conserved RBD residues and retains binding to the RBD of the Alpha,Beta,Gamma,Delta,Delta plus,Kappa,Lambda,Omicron BA.1,and BA.2 variants.In contrast,aRBD-5 and aRBD-7 bind to less conserved RBD epitopes non overlapping with the epitope of aRBD 2,and do not show apparent binding to the RBD of some variants.However,when fused with aRBD-2,they effectively enhance the overal binding affinity.Consistently,aRBD-2-5-Fc and aRBD-2-7 Fc potently neutralized all of the tested authentic or pseudotyped viruses,incuding WT,Alpha,Beta,Gamma,Delta,and Omicron BA.1,BA.1.1 and BA.2.Furthermore,aRBD-2-5-FC provided prophylactic protection against the WT and mouse-adapted SARS CoV-2 in mice,and conferred protection against the Omicron BA.1 variant in hamsters prophylatically and therapeutically,indicating that aRBD-2-5-Fc could potentially beneft the prevention and treatment of COVID-19 caused by the emerging variants of concern.Our strategy provides new solutions in the development of broad-spectrum therapeutic antibodies for COVID-19.

关 键 词：prevention spectrum continued 

分 类 号：R37[医药卫生—病原生物学]