Identification of potential phytochemicals from Citrus Limon against main protease of SARS-CoV-2: molecular docking, molecular dynamic simulations and quantum computations

Abstract

The outbreak of coronavirus disease (COVID-19) caused by a novel RNA virus emerged at the end of 2019. Most of the patient’s symptoms are mild to moderate, and influenza, acute respiratory distress syndrome (ARDS) and multi-organ failure are common. The disease is mild to moderate in most patients and is reported in many cases such as pneumonia, ARDS and multi-organ dysfunction. This study’s objective is to evaluate 25 natural compounds from Citrus limon (CL) used by comprehensive molecular docking, density functional theory (DFT) and molecular dynamics analysis against SARS-CoV-2 main protease (M^pro). Among all the experimental compounds, diosmetin has shown the best docking values against the M^pro of SARS-CoV-2 compared to the standard antiviral drug. In DFT calculations, the order associated with biochemical reactivity is as follows: eriodictoyl > quercetin > spinacetin > diosmetin > luteolin > apigenin, whereas the regions of oxygen and hydrogen atoms from the selected isolated compounds are appropriate for electrophilic and nucleophilic attacks, respectively. Also, HOMO-LUMO and global descriptors values indicated a promising result of these compounds. Moreover, a molecular dynamics simulation study revealed the stable conformation and binding pattern in a stimulating environment of natural compounds CL. Considering molecular docking, simulation, and DFT analysis of the selected compounds, notably eriodictoyl, quercetin, and diosmetin showed good potential against SARS-CoV-2 M^pro. Our in silico study revealed promising antiviral activity, which may be considered a potential key factor or a therapeutic target for COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Citrus limon
• SARS-CoV-2
• M^pro
• molecular docking
• DFT
• molecular dynamics

Acknowledgments

The authors are grateful to the Department of Theoretical and Computational Chemistry, University of Dhaka, Dhaka–1000, Bangladesh, for providing support and research facilities to accomplish this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

J.K. contributed to conceptualization, planning, designing, investigation, data analysis, software, manuscript writing and molecular docking; S.A.S. contributed to planning, designing, investigation, data analysis, data curation, software, manuscript writing and DFT calculations; S.M. contributed to designing, investigation, data analysis and molecular dynamic simulation; Z.K. rewrote and provided data analysis; M.N.I. contributed to planning, designing, investigation, manuscript and review writing; T.B.E., and J.S.G. together contributed to editing, review and correspondence. All authors have read and agreed to the published version of the manuscript.