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

查看全文 作　　者：Huan [1]Ma;Xinghai [2]Zhang;Peiyi [3]Zheng;Peter [4]H.Dube;Weihong [3]Zeng;Shaohong [2,5]Chen;Qingyu [3]Cheng;Yunru [3]Yang;Yan [2]Wu;Junhui [2,5]Zhou;Xiaowen [1]Hu;Yan [4]Xiang;Huajun [2]Zhang;Sandra [3]Chiu;Tengchuan [1,3,6]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》索引2022年第32卷第9期,共12页

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

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

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