부산대학교 도서관

Keywords COVID-19; SARS-CoV-2; monoclonal antibody; neutralizing antibody; crystal structures; autoreactivity; self-reactivity; self-antigens; hamster model; post-exposure Highlights * Characterization of potent human monoclonal SARS-CoV-2-neutralizing antibodies * Some SARS-CoV-2 antibodies reacted with mammalian self-antigens in different organs * Crystal structures of two antibodies in complex with SARS-CoV-2 RBD at 2.55/2.70 A * Post-exposure antibody treatment protected from lung damage in infected hamsters Summary The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC.sub.50 value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.