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Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains.
<div class='caption-title'>VH F6 binds to prevalent RBD mutants and neutralizes SARS-CoV-2 VOCs including Omicron BA.1 and BA.2</div>
<div class='caption-title'>CryoEM structure of VH F6 in complex with the SARS-CoV-2 Beta variant spike protein</div>
Chen C, Saville JW, Marti MM, Schäfer A, Cheng MH, Mannar D, Zhu X, Berezuk AM, Banerjee A, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Enick N, McCormick KD, Liu X, Adams C, Hines MG, Sun Z, Chen W, Jacobs JL, Barratt-Boyes SM, Mellors JW, Baric RS, Bahar I, Dimitrov DS, Subramaniam S, Martinez DR, Li W
OpenAccess logo iScience 25 104798 (2022)
Cited: 2 times
EuropePMC logo PMID: 35875685

Abstract

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human VH domain, F6, which we generated by sequentially panning large phage-displayed VH libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized VH domain, resulted in a construct (F6-ab8-Fc) that broadly and potently neutralized VOCs including Omicron. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 variants including Omicron and highlight a vulnerable epitope within the spike that may be exploited to achieve broad protection against circulating variants.

Articles - 8di5 mentioned but not cited (1)

  1. Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains. Chen C, Saville JW, Marti MM, Schäfer A, Cheng MH, Mannar D, Zhu X, Berezuk AM, Banerjee A, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Enick N, McCormick KD, Liu X, Adams C, Hines MG, Sun Z, Chen W, Jacobs JL, Barratt-Boyes SM, Mellors JW, Baric RS, Bahar I, Dimitrov DS, Subramaniam S, Martinez DR, Li W. iScience 25 104798 (2022)


Articles citing this publication (1)

  1. Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2. Longsompurana P, Rungrotmongkol T, Plongthongkum N, Wangkanont K, Wolschann P, Poo-Arporn RP, Poo-Arporn RP. PLoS One 18 e0293263 (2023)


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