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A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy.

<div class='caption-title'>Ab08 neutralizes SARS-CoV-2 Omicron-included variants and binds to RBD with pico-molar affinities.</div>
<div class='caption-title'>Ab08 shows therapeutic efficacy in hACE2 mice infected with live SARS-CoV-2.</div>
<div class='caption-title'>Structural characterization informs mechanism for the relatively broad activity of Ab08.</div>
Meng L, Zha J, Zhou B, Cao L, Jiang C, Zhu Y, Li T, Lu L, Zhang J, Yang H, Feng J, Gu Z, Tang H, Jiang L, Li D, Lavillette D, Zhang X
OpenAccess logo PLoS Pathog 19 e1011085 (2023)
Cited: 5 times
EuropePMC logo PMID: 36706160

Abstract

Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the β-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.

Reviews citing this publication (1)

  1. Is there any revival of the use of plasma therapy or neutralizing convalescent antibody therapy to treat SARS-CoV-2 variants and are we rethinking preparedness plans? Garraud O, Watier H. Transfus Apher Sci 62 103726 (2023)

Articles citing this publication (4)

  1. A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity. de Campos-Mata L, Trinité B, Modrego A, Tejedor Vaquero S, Pradenas E, Pons-Grífols A, Rodrigo Melero N, Carlero D, Marfil S, Santiago C, Raïch-Regué D, Bueno-Carrasco MT, Tarrés-Freixas F, Abancó F, Urrea V, Izquierdo-Useros N, Riveira-Muñoz E, Ballana E, Pérez M, Vergara-Alert J, Segalés J, Carolis C, Arranz R, Blanco J, Magri G. Nat Commun 15 1051 (2024)
  2. Structure-Based Design of Potent Peptidomimetic Inhibitors Covalently Targeting SARS-CoV-2 Papain-like Protease. Wang Q, Chen G, He J, Li J, Xiong M, Su H, Li M, Hu H, Xu Y. Int J Mol Sci 24 8633 (2023)
  3. Novel Competitive ELISA Utilizing Trimeric Spike Protein of SARS-CoV-2, Could Identify More Than RBD-RBM Specific Neutralizing Antibodies in Hybrid Sera. Eliadis P, Mais A, Papazisis A, Loxa EK, Dimitriadis A, Sarrigeorgiou I, Backovic M, Agallou M, Zouridakis M, Karagouni E, Lazaridis K, Mamalaki A, Lymberi P. Vaccines (Basel) 12 914 (2024)
  4. Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation. Chen Y, Zha J, Xu S, Shao J, Liu X, Li D, Zhang X. Viruses 16 566 (2024)


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