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Small Methods . A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape

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  • Small Methods . A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape


    Small Methods


    . 2022 May 18;e2200387.
    doi: 10.1002/smtd.202200387. Online ahead of print.
    A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape


    Bo Feng 1 2 , Zhilong Chen 3 4 , Jing Sun 1 , Tingting Xu 5 , Qian Wang 1 , Haisu Yi 1 , Xuefeng Niu 1 , Jiabin Zhu 1 , Mengzhu Fan 3 , Ruitian Hou 5 , Ying Shao 3 , Sihui Huang 3 , Cuiyun Li 5 , Peiyu Hu 2 , Pingqian Zheng 2 , Ping He 5 , Jia Luo 4 , Qihong Yan 5 , Xiaoli Xiong 5 , Jinsong Liu 5 , Jincun Zhao 1 2 , Ling Chen 1 2 3 5



    Affiliations

    Abstract

    The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.

    Keywords: SARS-CoV-2; neutralization; receptor binding domain (RBD); variants of concerns (VOCs).

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