Abstract
Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma, Delta and Omicron variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.
Keywords: COVID-19; SARS-CoV-2; VHH; VOC; nanobodies; neutralizing antibodies; single-domain antibodies.
【저자키워드】 COVID-19, SARS-CoV-2, Neutralizing antibodies, VoC, nanobodies, single-domain antibodies, VHH, 【초록키워드】 Treatment, antibodies, Neutralizing antibodies, antibody, SARS-CoV-2 variant, Delta, SARS-CoV-2 virus, omicron, virus, Omicron variants, variants, sensitivity, Neutralizing activity, Receptor-binding domain, nanobodies, Evolution of SARS-CoV-2, Gamma, Alpha, Beta, Neutralizing, virus variants, antibody-based therapies, S glycoprotein, broad spectrum, neutralization potency, virus-neutralizing antibodies, drug candidate, Modification, SARS-CoV-2 S glycoprotein, neutralized, robust, selected, caused, generate, reduced, were used, the receptor-binding domain, increase in, exhibiting, dimeric, heterodimeric, treatment for COVID-19, virus variant, 【제목키워드】 concern,