Coronavirus

2019-20 coronavirus outbreak

Molecular biology

Biology

Betacoronavirus

Virology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Neutralizing antibody

Coronavirus disease 2019 (COVID-19)

Immunology

Monoclonal antibody

Antigen

Hamster

Infectious disease (medical specialty)

Internal medicine

Medicine

Epitope

Virus

Pandemic

Disease

Antibody

Lung

Pathology

Cell

<h2>Summary</h2> 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</sub> 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 Å 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.

A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model