Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study.

Anuj Kumar,Rashmi Yadav,Dwijesh Chandra Mishra,Ulavappa Basavanneppa Angadi,Dinesh Kumar,Anil Rai

doi:10.3389/fchem.2021.744376

Abstract

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has now spread across the nations with high mortality rates and multifaceted impact on human life. The proper treatment methods to overcome this contagious disease are still limited. The main protease enzyme (Mpro, also called 3CLpro) is essential for viral replication and has been considered as one of the potent drug targets for treating COVID-19. In this study, virtual screening was performed to find out the molecular interactions between 36 natural compounds derived from sesame and the Mpro of COVID-19. Four natural metabolites, namely, sesamin, sesaminol, sesamolin, and sesamolinol have been ranked as the top interacting molecules to Mpro based on the affinity of molecular docking. Moreover, stability of these four sesame-specific natural compounds has also been evaluated using molecular dynamics (MD) simulations for 200 nanoseconds. The molecular dynamics simulations and free energy calculations revealed that these compounds have stable and favorable energies, causing strong binding with Mpro. These screened natural metabolites also meet the essential conditions for drug likeness such as absorption, distribution, metabolism, and excretion (ADME) properties as well as Lipinski’s rule of five. Our finding suggests that these screened natural compounds may be evolved as promising therapeutics against COVID-19.

Highlights

The ongoing pandemic eruption due to the worldwide spread of coronavirus disease (COVID-19) is caused by the novel virus strain severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; previously named 2019-nCoV) (Wu et al, 2020b)
There is no effective cure for COVID-19 so far; identification of potential drug compounds is required on an urgent basis
Representation of different types of interactions with sesamin including van der Waals, conventional hydrogen bond, carbon hydrogen bond, Pi–sigma, and alkyl; (E) hydrophobicity surface representation of the overall structure of Mpro in complex with Sesamin; and (F) pocket view of sesamin binding with Mpro and the representation of residues involved in hydrogen bond donor acceptor

Summary

Introduction

The ongoing pandemic eruption due to the worldwide spread of coronavirus disease (COVID-19) is caused by the novel virus strain severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; previously named 2019-nCoV) (Wu et al, 2020b). This viral disease is an unprecedented global public health care threat (Jamwal et al, 2020). The fatality rate of SARS-CoV and MERS has been calculated as 10 and 35%, respectively (Lee et al, 2004; Cheng et al, 2007) It has been well-reported that COVID-19 affects the lower respiratory tract of the body, which causes pneumonia and affects the gastrointestinal system, kidney, heart, and central nervous system. Cough, diarrhea, and tiredness have been considered the most common symptoms (Chen et al, 2020a; Tang et al, 2020), while aches and pains, sore throat, conjunctivitis, headache, loss of taste or smell, a rash on skin, or discoloration of fingers or toes are the less common symptoms of this infectious disease (Backer et al, 2020; Rothe et al, 2020; Russell et al, 2020; Verdoni et al, 2020; Yu and Yu, 2020)

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