Abstract
The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives of over 3.9 million people globally, at the time of this publication. Neutralizing humanized nanobody (V H H)-based antibodies (V H H-huFc) represent a promising therapeutic intervention strategy to address the current SARS-CoV-2 pandemic and provide a powerful toolkit to address future virus outbreaks. Using a synthetic, high-diversity V H H bacteriophage library, several potent neutralizing V H H-huFc antibodies were identified and evaluated for their capacity to tightly bind to the SARS-CoV-2 receptor-binding domain, to prevent binding of SARS-CoV-2 spike (S) to the cellular receptor angiotensin-converting enzyme 2, and to neutralize viral infection. Preliminary preclinical evaluation of multiple V H H-huFc antibody candidates demonstrate that they are prophylactically and therapeutically effective in vivo against wildtype SARS-CoV-2. The identified and characterized V H H-huFc antibodies described herein represent viable candidates for further preclinical evaluation and another tool to add to our therapeutic arsenal to address the COVID-19 pandemic.
Keywords: COVID-19; Nanobody; SARS-CoV-2; neutralizing antibody; phage display.
【저자키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, nanobody, phage display., 【초록키워드】 coronavirus disease, viral infection, coronavirus, antibody, SARS-CoV-2 pandemic, COVID-19 pandemic, virus, angiotensin-converting enzyme 2, Outbreaks, respiratory virus, therapeutic, Neutralizing, in vivo, binding, SARS-CoV-2 spike, acute respiratory syndrome, domain, candidate, therapeutic intervention, wildtype, toolkit, cellular receptor, humanized, Prevent, effective, neutralize, responsible, described, affected, evaluated, characterized, prophylactically, the SARS-CoV-2, 【제목키워드】 Neutralizing, development, effective,