Summary
The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.
【저자키워드】 neutralizing antibody, SARS-CoV-2, coronavirus, Spike protein, SARS-CoV-2 variants, RBD, phage display, recombinant antibody, immune library, in vivo neutralization, 【초록키워드】 COVID-19, Treatment, coronavirus disease, Efficacy, ACE2, clinical trial, severe COVID-19, antibody, IC50, hACE2, anti-SARS-CoV-2 antibodies, Neutralization assay, mice, Neutralizing, severe pneumonia, in vivo, disease, moderate, binding, Fab, RBD mutations, phase, complex, novel Betacoronavirus, human Angiotensin-converting enzyme, live SARS-CoV-2, SARS-CoV-2-RBD, scFv, human IgG1, bind, selected, blocked, develop, the spike protein, demonstrated, the receptor-binding domain, antibody fragment, cause, convalescent COVID-19 patient, 【제목키워드】 SARS-CoV-2 neutralizing antibody, COVID-19 patient, ACE2-RBD, RBD mutation, bind, selected,