Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC 50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC 50 within 10 nM, and the best one, 414-1, with IC 50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates. Graphical Abstract Wan et al. identify 11 potent neutralizing antibodies against COVID-19 from 11 convalescent patients. These human neutralizing antibodies target three separate epitopes on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, and epitope-B antibody (553-15) can enhance the neutralizing abilities of most other antibodies.