COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases. Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.
【저자키워드】 SARS-CoV-2, Antibody therapy, X-ray crystallography, 【초록키워드】 COVID-19, Treatment, neutralizing antibody, SARS-CoV2, Diseases, spike, antibody, Antibody-dependent enhancement, COVID-19 pandemic, Infection, monoclonal antibodies, viral clearance, Spike protein, Health crisis, Protein, Consequences, Neutralizing activity, Convalescent patients, Vulnerable populations, Viral, SARS-CoV-2 spike protein, spike receptor-binding domain, mutant, crystal structure, wild type, receptor binding motif, safety profile, convalescent patient, binding, SARS-CoV-2 S protein, pharmacokinetic, Analysis, Spike proteins, High-resolution, pseudoviruses, related diseases, global public health, These data, complex, therapeutic efficacy, potential risk, injection, enhancement, rhesus, antibodies binding, Complete, populations, COVID-19 convalescent patients, highlight, shown, caused, majority, interact, reduce, exhibit, the Spike, 【제목키워드】 spike, outcome, Coverage, therapeutic, SARS-CoV-2 neutralizing antibody, binding,