PMID- 33532909
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210315
IS  - 2193-8229 (Print)
IS  - 2193-6382 (Electronic)
IS  - 2193-6382 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Mar
TI  - Computational and Experimental Studies Reveal That Thymoquinone Blocks the Entry 
      of Coronaviruses Into In Vitro Cells.
PG  - 483-494
LID - 10.1007/s40121-021-00400-2 [doi]
AB  - 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 muM, 
      respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic 
      concentration of 35.100 muM and selection index = 7.020. CONCLUSION: Thymoquinone 
      is a potential broad-spectrum inhibitor for the treatment of coronavirus 
      infections.
FAU - Xu, Huan
AU  - Xu H
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
AD  - Shenzhen Bay Laboratories, Institute of Chemical Biology, Shenzhen, 518132, 
      China.
FAU - Liu, Bing
AU  - Liu B
AD  - Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei 
      Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, 
      050024, Hebei, China.
FAU - Xiao, Zhen
AU  - Xiao Z
AD  - Department of Biology, Southern University of Science and Technology, Shenzhen, 
      518055, Guangdong, China.
AD  - Guangdong Provincial Key Laboratory of Computational Science and Material Design, 
      Shenzhen, 518055, Guangdong, China.
FAU - Zhou, Meiling
AU  - Zhou M
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
FAU - Ge, Lin
AU  - Ge L
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
FAU - Jia, Fan
AU  - Jia F
AD  - 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.
AD  - Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 
      Shenzhen, 518055, China.
AD  - Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research 
      Institutions, Shenzhen, 518055, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
FAU - Liu, Yanling
AU  - Liu Y
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
FAU - Jin, Hongshan
AU  - Jin H
AD  - Nanjing Gemni Biotechnology Co., Ltd, Nanjing, 210023, China.
FAU - Zhu, Xiuliang
AU  - Zhu X
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
FAU - Gao, Jian
AU  - Gao J
AD  - New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 
      050015, China.
FAU - Akhtar, Javed
AU  - Akhtar J
AD  - Department of Biology, Southern University of Science and Technology, Shenzhen, 
      518055, Guangdong, China.
AD  - Guangdong Provincial Key Laboratory of Computational Science and Material Design, 
      Shenzhen, 518055, Guangdong, China.
FAU - Xiang, Bai
AU  - Xiang B
AD  - School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 
      050017, China. baixiang@hebmu.edu.cn.
FAU - Tan, Ke
AU  - Tan K
AD  - 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.
FAU - Wang, Guanyu
AU  - Wang G
AUID- ORCID: 0000-0002-8229-6559
AD  - Department of Biology, Southern University of Science and Technology, Shenzhen, 
      518055, Guangdong, China. wanggy@sustech.edu.cn.
AD  - Guangdong Provincial Key Laboratory of Computational Science and Material Design, 
      Shenzhen, 518055, Guangdong, China. wanggy@sustech.edu.cn.
LA  - eng
GR  - 2017ZX09303008/National Science and Technology Major Project/
GR  - 81973251/National Natural Science Foundation of China/
GR  - 61773196/National Natural Science Foundation of China/
GR  - 32070681/National Natural Science Foundation of China/
GR  - H2019206445/Natural Science Foundation of Hebei Province/
GR  - 2020KZDZX1182/Guangdong Special Projects on COVID-19/
GR  - 2019B030301001/Guangdong Provincial Key Laboratory of Computational Science and 
      Material Design/
GR  - JCYJ20170817104740861/Shenzhen Research Funds/
GR  - KQTD2016053117035204/Shenzhen Peacock Plan/
PT  - Journal Article
DEP - 20210202
PL  - New Zealand
TA  - Infect Dis Ther
JT  - Infectious diseases and therapy
JID - 101634499
PMC - PMC7853165
OTO - NOTNLM
OT  - Broad-spectrum inhibitor
OT  - Coronavirus
OT  - NL63-CoV
OT  - SARS-CoV
OT  - SARS-CoV-2
OT  - Thymoquinone
EDAT- 2021/02/04 06:00
MHDA- 2021/02/04 06:01
PMCR- 2021/02/02
CRDT- 2021/02/03 06:02
PHST- 2020/10/12 00:00 [received]
PHST- 2021/01/09 00:00 [accepted]
PHST- 2021/02/04 06:00 [pubmed]
PHST- 2021/02/04 06:01 [medline]
PHST- 2021/02/03 06:02 [entrez]
PHST- 2021/02/02 00:00 [pmc-release]
AID - 10.1007/s40121-021-00400-2 [pii]
AID - 400 [pii]
AID - 10.1007/s40121-021-00400-2 [doi]
PST - ppublish
SO  - Infect Dis Ther. 2021 Mar;10(1):483-494. doi: 10.1007/s40121-021-00400-2. Epub 
      2021 Feb 2.