Structure-based identification of potential SARS-CoV-2 main protease inhibitors.

Journal of Biomolecular Structure & Dynamics
Shama KhanMd Imtaiyaz Hassan

Abstract

To address coronavirus disease (COVID-19), currently, no effective drug or vaccine is available. In this regard, molecular modeling approaches are highly useful to discover potential inhibitors of the main protease (Mpro) enzyme of SARS-CoV-2. Since, the Mpro enzyme plays key roles in mediating viral replication and transcription; therefore, it is considered as an attractive drug target to control SARS-CoV-2 infection. By using structure-based drug design, pharmacophore modeling, and virtual high throughput drug screening combined with docking and all-atom molecular dynamics simulation approach, we have identified five potential inhibitors of SARS-CoV-2 Mpro. MD simulation studies revealed that compound 54035018 binds to the Mpro with high affinity (ΔGbind -37.40 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. We have identified promising leads to fight COVID-19 infection as these compounds fulfill all drug-likeness properties. However, experimental and clinical validations are required for COVID-19 therapy.Communicated by Ramaswamy H. Sarma.

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Citations

Feb 21, 2021·Biomedical Journal·Paola MagroEugenia Quiros-Roldan
Jan 6, 2021·The FEBS Journal·Chun-Chi ChenRey-Ting Guo
Mar 4, 2021·Journal of Ayurveda and Integrative Medicine·Thrigulla Saketh RamK S Dhiman
Jul 25, 2020·Journal of Biomolecular Structure & Dynamics·Nima Razzaghi-AslDanial Gholamin
Aug 4, 2020·Journal of Biomolecular Structure & Dynamics·Pradeep SharmaSujata Sharma
Sep 3, 2020·Journal of Biomolecular Structure & Dynamics·Babatunde Joseph OsoIge Francis Olaoye
May 26, 2020·Journal of Biomolecular Structure & Dynamics·Anuj KumarMadhu Rathore
Sep 3, 2021·Biotechnology & Genetic Engineering Reviews·Soumya BasuAnand Anbarasu
Jul 9, 2021·Journal of Cellular Biochemistry·Mohd UmairMd Imtaiyaz Hassan
Nov 10, 2021·Journal of Cellular Biochemistry·Saleha AnwarMd Imtaiyaz Hassan

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Software Mentioned

SASA
AMBER
Epik
Origin
Protein Preparation Wizard
LigPrep
QikProp
PHASE
CPPTRAJ
General Amber Force - Field ( GAFF )

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