In silico screening of Pueraria tuberosa (PTY-2) for targeting COVID-19 by countering dual targets M^pro and TMPRSS2

Abstract

COVID-19 pandemic was started in Wuhan city of China in December 2019; immensely affected global population. Herein, an effort was made to identify potential inhibitors from active phytochemicals of Pueraria tuberosa (PTY-2) via molecular docking study. Our study showed five potential inhibitors (Robinin, Genistin, Daidzin, Hydroxytuberosone, Tuberostan) against M^pro and five inhibitors (Robinin, Anhydrotuberosin, Daidzin, Hydroxytuberosone, Stigmasterol) against TMPRSS2. Out of these, Robinin, Daidzin and Hydroxytuberosone were common inhibitors for M^pro and TMPRSS2. Among these, Robinin showed the highest binding affinity, therefore, tested for MD simulation runs and found stable. ADMET analysis revealed the best-docked compounds are safe and follow the Lipinski Rule of Five. Thus, it could be suggested that phytochemicals of PTY-2 could serve as potential inhibitors for COVID-19 targets.

Communicated by Ramaswamy H. Sarma

Highlights

• Application of active phytoconstituents of Pueraria tuberosa (PTY-2) for the repurposing in the management of COVID-19.

• Promising effect of Robinin as a multifocal inhibitor of virus-host interaction including main protease (M^pro) and TMPRSS2 with highest binding energy through molecular docking and molecular dynamics simulations studies.

• Robinin acts as common inhibitor against M^pro and TMPRSS2.

Keywords:

• COVID-19
• M^pro
• TMPRSS2
• Robinin
• ADMET
• drug-likeness

Acknowledgements

The authors thank BHU administration, Center for Bioinformatics, School of Biotechnology, Department of Biotechnology, Institute of Sciences, Banaras Hindu University, Varanasi, India for the use of YASARA software. Manish Singh, Department of Pharmacology, IMS, BHU for image correction. Authors thank HPC facility of IIT Mandi for simulation studies.

Disclosure statement

Authors declare no conflict of interest.

Author’s contribution

Study conception and design by Prof. Yamini Bhusan Tripathi and Priya Shree. Acquisition, analysis and interpretation of data were done by Priya Shree. Drafting of manuscript were done by Priya Shree, Priyanka Mishra and Harsh Pandey. Prateek Kumar and Rajanish Giri performed the MD simulations and contributed to writing of the manuscript. Critical revision was done by Prof. Yamini Bhusan Tripathi, Dr. Radha Chaube and Dr. Neha Garg.

Additional information

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.