Xu Huan, Liu Bing, Xiao Zhen, Zhou Meiling, Ge Lin, Jia Fan, Liu Yanling, Jin Hongshan, Zhu Xiuliang, Gao Jian, Akhtar Javed, Xiang Bai, Tan Ke, Wang Guanyu
New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 050015, China.
Shenzhen Bay Laboratories, Institute of Chemical Biology, Shenzhen, 518132, China.
Infect Dis Ther. 2021 Mar;10(1):483-494. doi: 10.1007/s40121-021-00400-2. Epub 2021 Feb 2.
Since December 2019, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in China and worldwide. New drugs for the treatment of COVID-19 are in urgent need. Considering the long development time for new drugs, the identification of promising inhibitors from FDA-approved drugs is an imperative and valuable strategy. Recent studies have shown that the S1 and S2 subunits of the spike protein of SARS-CoV-2 utilize human angiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells.
We combined molecular docking and surface plasmon resonance (SPR) to identify potential inhibitors for ACE2 from available commercial medicines. We also designed coronavirus pseudoparticles that contain the spike protein assembled onto green fluorescent protein or luciferase reporter gene-carrying vesicular stomatitis virus core particles.
We found that thymoquinone, a phytochemical compound obtained from the plant Nigella sativa, is a potential drug candidate. SPR analysis confirmed the binding of thymoquinone to ACE2. We found that thymoquinone can inhibit SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles infecting HEK293-ACE2 cells, with half-maximal inhibitory concentrations of 4.999, 7.598, and 6.019 μM, respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic concentration of 35.100 μM and selection index = 7.020.
Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.
自2019年12月以来，严重急性呼吸综合征相关冠状病毒2（SARS-CoV-2）在中国及全球引发了2019冠状病毒病（COVID-19）大流行。治疗COVID-19的新药亟待研发。考虑到新药研发时间较长，从美国食品药品监督管理局（FDA）批准的药物中筛选出有前景的抑制剂是一项必要且有价值的策略。最近的研究表明，SARS-CoV-2刺突蛋白的S1和S2亚基利用人类血管紧张素转换酶2（hACE2）作为受体来感染人类细胞。
我们结合分子对接和表面等离子体共振（SPR）技术，从现有商业药物中筛选出潜在的ACE2抑制剂。我们还设计了冠状病毒假颗粒，其包含组装在携带绿色荧光蛋白或荧光素酶报告基因的水疱性口炎病毒核心颗粒上的刺突蛋白。
我们发现从植物黑种草中提取的植物化学化合物百里醌是一种潜在的候选药物。SPR分析证实了百里醌与ACE2的结合。我们发现百里醌可以抑制SARS-CoV-2、SARS-CoV和NL63假颗粒感染HEK293-ACE2细胞，其半数最大抑制浓度分别为4.999、7.598和6.019μM。对SARS-CoV-2假颗粒的抑制作用中，半数最大细胞毒性浓度为35.100μM，选择指数=7.020。
百里醌是一种潜在的治疗冠状病毒感染的广谱抑制剂。
