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Updated: Nov 19, 2025
Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Computational and Experimental Studies Reveal That Thymoquinone Blocks the Entry of Coronaviruses Into In Vitro Cells
Huan Xu1,2, Bing Liu3, Zhen Xiao4,5
1New Drug R&D Center, North China Pharmaceutical Corporation, Shijiazhuang, 050015, China.
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.
Insights
Thymoquinone, derived from Nigella sativa, shows potential as a broad-spectrum antiviral drug. It effectively inhibits SARS-CoV-2 and other coronaviruses by binding to the ACE2 receptor, offering a promising treatment strategy.
Area of Science:
- Virology
- Drug Discovery
- Biochemistry
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates urgent development of new treatments.
- Identifying inhibitors from existing FDA-approved drugs is a valuable strategy due to lengthy drug development timelines.
- SARS-CoV-2 infects human cells by utilizing the S1 and S2 subunits of its spike protein to bind with the human angiotensin-converting enzyme 2 (hACE2) receptor.
Purpose of the Study:
- To identify potential inhibitors of the ACE2 receptor from commercially available medicines.
- To evaluate the efficacy of identified compounds against coronavirus infections.
Main Methods:
- Molecular docking and surface plasmon resonance (SPR) were employed to screen for ACE2 inhibitors.
- Coronavirus pseudoparticles displaying the SARS-CoV-2 spike protein were generated for in vitro testing.
- HEK293-ACE2 cells were used to assess the inhibitory activity of compounds against viral pseudoparticle entry.
Main Results:
- Thymoquinone, a phytochemical from Nigella sativa, was identified as a potential drug candidate.
- SPR analysis confirmed direct binding of thymoquinone to ACE2.
- Thymoquinone demonstrated inhibitory effects against SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles with IC50 values ranging from 4.999 to 7.598 μM.
- For SARS-CoV-2, thymoquinone exhibited a half-maximal cytotoxic concentration (CC50) of 35.100 μM, resulting in a favorable selection index of 7.020.
Conclusions:
- Thymoquinone is a potential broad-spectrum inhibitor for treating various coronavirus infections.
- Its ability to inhibit viral entry via the ACE2 receptor makes it a promising therapeutic agent.
