Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.
【초록키워드】 COVID-19, SARS-CoV-2, Efficacy, Vaccine, coronavirus, Mutation, variant, SARS-CoV-2 variant, B.1.617.2, in vitro, novel coronavirus disease, SARS-CoV-2 vaccine, global pandemic, RBD, Microscopy, VOCs, cryo-EM, in vivo, epitope, mAbs, neutralizing monoclonal antibody, mAb, Clinical use, acute respiratory syndrome, molecular basis, treat, wild-type, circulating, Prevent, neutralize, caused, approved, reduced, unique, demonstrated, the receptor-binding domain, 【제목키워드】 SARS-CoV-2, activity, RBD, Human monoclonal antibody, binding, S trimer, form,