The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
【초록키워드】 COVID-19, Treatment, neutralizing antibody, SARS-CoV-2, Vaccine, SARS-CoV, COVID-19 pandemic, lung, public health crisis, hACE2, Receptor binding domain, Epitopes, pseudovirus, RBD, receptors, epitope, cellular, administration, Analysis, Pulmonary pathology, host cell, Virological, complex, therapeutic intervention, treating COVID-19, Fab fragment, humanized monoclonal antibody, Prevent, neutralize, S trimer, highlight, caused, reported, approved, reduced, demonstrated, against SARS-CoV, the RBD, conformational, prevented, cross-protective, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 SARS-CoV-2, antibody, SARS-CoV, neutralization, therapeutic,