Virtual screening, molecular dynamics and structure-activity relationship studies to identify potent approved drugs for Covid-19 treatment.

Journal of Biomolecular Structure & Dynamics
Md Mahbubur RahmanMohammad A Halim

Abstract

Computer-aided drug screening by molecular docking, molecular dynamics (MD) and structural-activity relationship (SAR) can offer an efficient approach to identify promising drug repurposing candidates for COVID-19 treatment. In this study, computational screening is performed by molecular docking of 1615 Food and Drug Administration (FDA) approved drugs against the main protease (Mpro) of SARS-CoV-2. Several promising approved drugs, including Simeprevir, Ergotamine, Bromocriptine and Tadalafil, stand out as the best candidates based on their binding energy, fitting score and noncovalent interactions at the binding sites of the receptor. All selected drugs interact with the key active site residues, including His41 and Cys145. Various noncovalent interactions including hydrogen bonding, hydrophobic interactions, pi-sulfur and pi-pi interactions appear to be dominant in drug-Mpro complexes. MD simulations are applied for the most promising drugs. Structural stability and compactness are observed for the drug-Mpro complexes. The protein shows low flexibility in both apo and holo form during MD simulations. The MM/PBSA binding free energies are also measured for the selected drugs. For pattern recognition, structural similarity an...Continue Reading

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Citations

Oct 14, 2020·Journal of Biomolecular Structure & Dynamics·Archi Sundar PaulMohammad A Halim
Sep 24, 2020·Archives of Medical Research·Krishnaprasad BabyYogendra Nayak
Mar 25, 2021·Journal of Biomolecular Structure & Dynamics·Birendra KumarVivek Chandramohan
May 23, 2021·Computers in Biology and Medicine·Md Mahbubur RahmanMohammad A Halim
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marco A Almaraz-GirónSandra L Castañón-Alonso
Aug 24, 2021·Cell & Bioscience·Azadeh SafarchiFatemeh Vafaee
Oct 9, 2021·Briefings in Bioinformatics·Qiaoming LiuGuohua Wang
Nov 6, 2021·ACS Synthetic Biology·Nícia Rosário-FerreiraIrina S Moreira

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Methods Mentioned

BETA
X-ray
PCA

Software Mentioned

GOLD
AutoDock
Autodock Vina
YASARA
YASARA Dynamics
PyRx Virtual Screening Tools
R
Gaussian
BIOVIA Discovery Studio Visualizer
ggplot2

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