Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S 470–495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S 450–458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic. Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.
【저자키워드】 antibodies, SARS-CoV-2, 【초록키워드】 COVID-19, viruses, Efficacy, Mutation, Neutralizing antibodies, spike, antibody, B.1.351, SARS-COV-2 infection, COVID-19 pandemic, monoclonal antibody, SARS-CoV-2 virus, in vitro, Prophylactic, monoclonal antibodies, virus, hACE2, Receptor binding domain, Prophylaxis, human ACE2, Protein, Immune escape, RBD, Neutralizing, cryo-EM, virus infection, E484K mutation, in vivo, mechanism, mAbs, SARS-CoV-2 spike, Structural analysis, weight loss, overlapping, Candidates, transgenic mice, candidate, authentic SARS-CoV-2 virus, treat, SARS-CoV-2 mutants, bind, virus, unique, recognize, reducing, the RBD, expressing, evidenced, steric, the SARS-CoV-2, 【제목키워드】 Efficacy, variant, potent, SARS-CoV-2 neutralizing antibody, Protective,