Related Experiment Video
Updated: Oct 26, 2025
Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Target-Based In Silico Screening for Phytoactive Compounds Targeting SARS-CoV-2
Yong Zhao1, Yu Tian2, Chenling Pan3
1Beijing Computing Center, Beijing Academy of Science and Technology, 7 Fengxian Road, Beijing, 100094, China. yongzhao168@gmail.com.
Insights
This study screened 33,765 herbal compounds against SARS-CoV-2 enzymes to find potential COVID-19 treatments. Researchers identified promising natural products that may inhibit viral replication, offering new avenues for drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Virology
Background:
- COVID-19, caused by SARS-CoV-2, poses a significant global health and economic burden.
- Existing treatments are insufficient, highlighting the need for novel prevention and therapeutic strategies.
- Herbal remedies show potential but lack clear mechanisms of action against SARS-CoV-2.
Purpose of the Study:
- To identify natural products from herbal remedies with anti-SARS-CoV-2 activity.
- To investigate potential antiviral mechanisms by targeting key viral enzymes.
- To provide a framework for developing new chemoprophylaxis agents against COVID-19.
Main Methods:
- In silico screening of 33,765 compounds from medicinal plants against four key SARS-CoV-2 enzymes.
- Target enzymes included Papain-like protease, Main protease, RNA dependent RNA polymerase, and 2 -O-ribose methyltransferase.
- Compounds were ranked based on binding affinity (free energy of fitting) to enzyme active sites.
Main Results:
- A list of potential antiviral ingredients from herbal sources targeting SARS-CoV-2 was generated.
- Analysis included plant origins and pharmacokinetic properties of the top-ranked compounds.
- Identified compounds show promise for inhibiting critical steps in the SARS-CoV-2 life cycle.
Conclusions:
- Computational screening identified promising natural compounds from herbal remedies with potential anti-SARS-CoV-2 activity.
- These compounds may act by inhibiting essential viral enzymes, offering a basis for further drug development.
- Further research into these natural products could lead to new preventative and therapeutic options for COVID-19.
Abstract:
Coronavirus disease 2019 (COVID-19), resulting from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause severe and fatal pneumonia along with other life-threatening complications. The COVID-19 pandemic has taken a heavy toll on the healthcare system globally and has hit the economy hard in all affected countries. As a result, there is an unmet medical need for both the prevention and treatment of COVID-19 infection. Several herbal remedies have claimed to show promising clinical results, but the mechanisms of action are not clear. We set out to identify the anti-viral natural products of these herbal remedies that presumably inhibit the life cycle of SARS-CoV-2. Particularly we chose four key SARS-CoV-2 viral enzymes as targets: Papain-like protease, Main protease, RNA dependent RNA polymerase, and 2'-O-ribose methyltransferase, which were subjected to an unbiased in silico screening against a small molecule library of 33,765 compounds originating from herbs and medicinal plants. The small molecules were then ranked based on their free energy of fitting into the "druggable" pockets on the surface of each target protein. We have analyzed the best "fit" molecules and annotated them according to their plant sources and pharmacokinetic properties. Here we present a list of potential anti-viral ingredients of herbal remedies targeting SARS-CoV-2 and explore the potential mechanisms of action of these compounds as a framework for further development of chemoprophylaxis agents against COVID-19.
