A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants

J Med Virol. 2023 Mar;95(3):e28657. doi: 10.1002/jmv.28657.


Novel immune escape variants have emerged as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose of mAb G5 could significantly inhibit the viral burden in mice challenged with the mouse-adapted SARS-CoV-2 or SARS-CoV-2 Omicron BA.1 variant, as well as the body weight loss and cytokine release induced by mouse-adapted SARS-CoV-2. The refined epitope recognized by mAb G5 was identified as 1148 FKEELDKYF1156 in the stem helix of subunit S2. In addition, a human-mouse chimeric mAb was generated based on the variable region of heavy chain and VL genes of mAb G5. Our study provides a broad antibody drug candidate against SARS-CoV-2 VOCs and reveals a novel target for developing pan-SARS-CoV-2 vaccines.

Keywords: SARS-CoV-2 VOCs; broadly protective epitope; neutralizing antibody; prophylactic and therapeutic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Neutralizing
  • Antibodies, Viral / therapeutic use
  • COVID-19 Vaccines
  • COVID-19*
  • Humans
  • Immunosuppressive Agents
  • Mice
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics


  • Antibodies, Monoclonal
  • COVID-19 Vaccines
  • Immunosuppressive Agents
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants