Laboratory of Functional and Molecular Imaging, The National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, MD, 20892, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20892, USA.
Sci Rep. 2020 Dec 22;10(1):22370. doi: 10.1038/s41598-020-79036-0.
There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1-5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.
目前，针对导致 COVID-19 大流行的 SARS-CoV-2 病毒，仅有少数经过批准的有效治疗方法。纳米抗体是 12-15 kDa 的单域抗体片段，可通过吸入方式给药，与其他生物制剂相比，其生产成本相对较低，易于大规模生产。我们已经分离出了与 SARS-CoV-2 刺突蛋白受体结合域结合的纳米抗体，并以 1-5 nM 的亲和力阻断刺突蛋白与血管紧张素转化酶 2（ACE2）的相互作用。领先的纳米抗体候选药物 NIH-CoVnb-112 可阻断表达人 ACE2 的 HEK293 细胞中 SARS-CoV-2 刺突假型慢病毒的感染，其 EC 为 0.3 µg/mL。NIH-CoVnb-112 在雾化后仍保持结构完整性和效力。此外，NIH-CoVnb-112 可阻断 ACE2 与几种高亲和力变异形式的刺突蛋白之间的相互作用。这些纳米抗体及其衍生物具有治疗、预防和诊断的潜力。
