Pomegranate peel polyphenols prophylaxis against SARS-CoV-2 main protease by in-silico docking and molecular dynamics study

Abstract

Pomegranate peel, the waste product generated from pomegranate fruit, has prophylactic properties, such as antimicrobial, anti-malarial, and controls respiratory infections and influenza. Based on the previous literature and need of the hour, molecular docking was performed to evaluate the inhibitory effects of major pomegranate peel polyphenols against COVID-19. Among the 44 studied compounds, 37 polyphenols show interaction with the catalytic dyad of the M^pro protease and 18 polyphenols have a higher binding affinity than that of the M^pro protease inhibitor (N3), indicating their high probability of binding at ACE2: SARS-CoV-2 interface. Furthermore, several polyphenols studied in this work are found to have higher binding affinity as compared to those of hydroxychloroquine, lopinavir, nelfinavir, and curcumin, some of which have been earlier tested against COVID-19. Further, molecular dynamics simulations (200 ns) for M^pro–polyphenols including pelargonidin3-glucoside, quercetin3-O-rhamnoside, cyanidin3-glucoside and punicalin revealed highly stable complexes with less conformational fluctuations and similar degree of compactness. Estimation of total number of intermolecular hydrogen bonds and binding free energy confirmed the stability of these M^pro–polyphenol complexes over M^pro–curcumin complex. Based on the greater binding affinity of polyphenols of pomegranate peel towards M^pro as compared to that of curcumin, pomegranate peel may be considered in any herbal medicinal formulation or may be incorporated into daily diets for prevention of COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anti-COVID-19
• flavonoids
• hydrolysable tannins
• herbal medicine
• immunity booster
• molecular dynamics simulation
• binding energy

Acknowledgements

The authors would like to thank Ms. Mandira Kapri, IIT Delhi, India for her technical support in the work. This work used the resources of the Paramshakti supercomputing facility of IIT Kharagpur established under the National Supercomputing Mission of Government of India and supported by CDAC, Pune.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

Madhulekha Rakshit and Prem Prakash Srivastav planned the research. Madhulekha Rakshit performed the docking studies. Sunita Muduli performed the molecular dynamics simulations and molecular dynamics analysis. Sabyashachi Mishra supervised the molecular dynamics studies. All authors contributed towards manuscript preparation.

Data availability statement

All the supporting data of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

M. Rakshit is thankful to Ministry of Human Resources Development, Government of India, for providing the services and financial assistance to conduct this study. S. Muduli acknowledges the financial support from UGC, New Delhi. S. Mishra acknowledges the support from SERB, DST, Govt. India (EMR/2015/001890 and SR/FST/CSII-026/2013) and CSIR, India (01(2987)/19/EMR-II).