Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.
【저자키워드】 Pattern recognition receptors, Cryoelectron microscopy, 【초록키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Mutation, Neutralizing antibodies, antibody, variant, Cryo-electron microscopy, Measures, antibody cocktail, RBD, therapeutic, death, Neutralizing, mutant, experiment, epitope mapping, group, epitope, strain, acute respiratory syndrome, Threats, residue, pandemic disease, Coronaviral, effective, performed, caused, involved, provide, the receptor-binding domain, evade, eliminated, 【제목키워드】 SARS-CoV-2, antibody, mice, mutant, neutralize,