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  3. Computational and Experimental Studies Reveal That Thymoquinone Blocks the Entry of Coronaviruses Into In Vitro Cells

Computational and Experimental Studies Reveal That Thymoquinone Blocks the Entry of Coronaviruses Into In Vitro Cells

  • Infect Dis Ther. 2021 Mar;10(1):483-494. doi: 10.1007/s40121-021-00400-2.
Huan Xu  # 1 2,  Bing Liu  # 3,  Zhen Xiao  # 4 5,  Meiling Zhou 1,  Lin Ge 1,  Fan Jia 6 7 8 9,  Yanling Liu 1,  Hongshan Jin 10,  Xiuliang Zhu 1,  Jian Gao 1,  Javed Akhtar 4 5,  Bai Xiang 11,  Ke Tan 12,  Guanyu Wang 13 14
Affiliations

Affiliations

  • 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.
  • # Contributed equally.
PMID: 33532909 DOI: 10.1007/s40121-021-00400-2
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.

Keywords

Broad-spectrum inhibitor; Coronavirus; NL63-CoV; SARS-CoV; SARS-CoV-2; Thymoquinone.

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