Huan Xu1,2, Bing Liu3, Zhen Xiao4,5, Meiling Zhou1, Lin Ge1, Fan Jia6,7,8,9, Yanling Liu1, Hongshan Jin10, Xiuliang Zhu1, Jian Gao1, Javed Akhtar4,5, Bai Xiang11, Ke Tan12, Guanyu Wang13,14. 1. New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 050015, China. 2. Shenzhen Bay Laboratories, Institute of Chemical Biology, Shenzhen, 518132, China. 3. Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, 050024, Hebei, China. 4. Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. 5. Guangdong Provincial Key Laboratory of Computational Science and Material Design, Shenzhen, 518055, Guangdong, China. 6. Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen, 518055, China. 7. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. 8. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China. 9. University of Chinese Academy of Sciences, Beijing, 100049, China. 10. Nanjing Gemni Biotechnology Co., Ltd, Nanjing, 210023, China. 11. School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China. baixiang@hebmu.edu.cn. 12. Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, 050024, Hebei, China. tanke@hebtu.edu.cn. 13. Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. wanggy@sustech.edu.cn. 14. Guangdong Provincial Key Laboratory of Computational Science and Material Design, Shenzhen, 518055, Guangdong, China. wanggy@sustech.edu.cn.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.
INTRODUCTION: 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 humanangiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells. METHODS: 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. RESULTS: 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. CONCLUSION:Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.
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