Ye Gang, Gallant Joseph P, Massey Christopher, Shi Ke, Tai Wanbo, Zheng Jian, Odle Abby E, Vickers Molly A, Shang Jian, Wan Yushun, Drelich Aleksandra, Kempaiah Kempaiah R, Tat Vivian, Perlman Stanley, Du Lanying, Tseng Chien-Te, Aihara Hideki, LeBeau Aaron M, Li Fang
Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.
Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
bioRxiv. 2020 Nov 17:2020.11.17.386532. doi: 10.1101/2020.11.17.386532.
Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking out viral receptor ACE2. The lead drug possessing an Fc tag ( ) bound to SARS-CoV-2 RBD with a K of 15.7picomolar (∼3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND of 0.16microgram/milliliter (∼6000 times more potently than ACE2 did). Administered at a single dose, demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of c documented a greater than 10-day half-life efficacy and high tissue bioavailability. is a potentially effective and realistic solution to the COVID-19 pandemic.
Potent and low-cost drugs block SARS-CoV-2 infections both and and act both preventively and therapeutically.
抗击新冠疫情需要高效且低成本的治疗方法。我们从骆驼科纳米抗体噬菌体展示文库中鉴定出了一系列新型单域抗体（即纳米抗体），Nanosota-1。结构数据显示，其与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白通常隐藏的受体结合域（RBD）结合，阻断病毒受体血管紧张素转换酶2（ACE2）。具有Fc标签（ ）的先导药物与SARS-CoV-2 RBD结合，解离常数（K ）为15.7皮摩尔（比ACE2紧密约3000倍），并以0.16微克/毫升的半数抑制浓度（ND ）抑制SARS-CoV-2感染（比ACE2有效约6000倍）。单次给药时，该药物在感染SARS-CoV-2的仓鼠中显示出预防和治疗效果。与传统抗体药物不同，它在细菌中高产，且具有出色的热稳定性。对该药物的药代动力学分析表明其半衰期超过10天，疗效显著且组织生物利用度高。该药物是应对新冠疫情的一种潜在有效且切实可行的解决方案。
高效且低成本的该药物在体内和体外均能阻断SARS-CoV-2感染，兼具预防和治疗作用。
