Title:Computational Approaches Molecular Docking and MD Simulation
Establishes the Potential COVID-19 Main Protease Inhibitors from
Natural Products
Volume: 4
Issue: 2
Author(s): Areesh Zehra, Raquibun Nisha, Abhishek Kumar, Durgesh Nandan, Iqrar Ahmad, Debarshi Kar Mahapatra, Harun Patel, Biswanath Maity and Pranesh Kumar*
Affiliation:
- Department of Pharmacology, Institute of Pharmaceutical Sciences, University of Lucknow,
Lucknow, 226031, Uttar Pradesh, India
Keywords:
COVID-19, natural products, SAR-CoV-2, SWISS-ADME, molecular docking, MD simulation.
Abstract:
Aim: COVID-19 was classified as a pandemic by the World Health Organization
(WHO) on March 11, 2020. No reliable cure, however, was found. To prevent viral replication,
complementary therapy with antiviral and antimalarial medications were used. However, due to
their synthetic origin, they have a lot of side effects. To overcome this bane natural origin drugs
were repositioned.
Background: As repositioned drugs do not undergo a pro-long process of pre-clinical trial, hence,
they play an excellent role in the spillover of pathogens. The main protease (6LU7) enzyme found
in severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is essential for viral replication.
Thus, it acts as a hotspot in drug discovery.
Objective: A molecular docking computational approach was used to determine the ability of the binding
contract between the selected 3D-models of COVID-19 protease target and proposed natural compounds
pristimerin, amazoquinone, kendomycin, celastrol, 20-epi-isoguesterinol, phenanthrenequinone,
taxodione, maytenoquinone, hippeastrine, ammothamnine, 28-hydroxy isoiguesterin, hemanthamine,
alisol-B, stigmasterol, β-pinene,and β-sitosterol through Autodock v.1.5.6 software.
Methods: The present study is designed to perform in-silico studies using molecular docking (Autodock
tool v.1.5.6), Discovery Studio 2017 R2 client, Patch dock, SWISS-ADME prediction, and
molecular simulation (Desmond simulation package of Schrodinger) between 6LU7 and natural
origin compounds.
Results: The results of docking study performed between 6LU7 and compounds pristimerin, amazoquinone,
kendomycin, celastrol, 20-epi-isoguesterinol, phenanthrenequinone, taxodione, maytenoquinone,
hippeastrine, ammothamnine, 28-hydroxy isoiguesterin, hemanthamine, alisol-B,
stigmasterol, β-pinene, and β-sitosterol, showed binding energy as -9.68, -7.34, -5.34, -4.63, -4.24,
-4.13, -4.08, -3.85, -3.83, -3.7, -3.6, -3.57, -3.54, -3.39, -3.18, and -3.03 Kcal/mol, respectively. It
can be shown that the Pristimerin-6LU7 protein complex was maintained throughout the simulation
since the ligand RMSDs varied with a maximum value of 4.2Å during the first 10 ns, followed
by more stable interactions for the remaining time of the simulation.
Conclusion: The goal of the current work was to find inhibitors for both prophylactic and
therapeutic usage in COVID-19 patients.
