Medical Microbiology Department, Federal State Budget Institution "National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Department of Genetics and Molecular Biology of Bacteria, Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Front Immunol. 2022 Feb 24;13:822159. doi: 10.3389/fimmu.2022.822159. eCollection 2022.
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.
病毒中和抗体是治疗 COVID-19 的少数方法之一。SARS-CoV-2 病毒的进化导致了一些对抗体为基础的治疗方法敏感性降低的病毒变异株的出现。急需开发具有广谱中和活性的强效抗体。在这里，我们分离出了一组能够特异性结合 SARS-CoV-2 S 糖蛋白受体结合域的单域抗体。选择了三个具有最强中和效力的抗体来生成二聚体分子。我们观察到这些修饰导致中和活性提高了 200 倍。最有效的杂二聚体分子有效地中和了所有关注的 SARS-CoV-2 变体，包括 Alpha、Beta、Gamma、Delta 和 Omicron 变体。这种杂二聚体分子可能是治疗由关注的病毒变体引起的 COVID-19 的有前途的候选药物。
