Title:In Silico Analysis of Drug Repurposing Strategy for the Identification of Potential NS3 Helicase Inhibitors Against Zika Virus
Volume: 1
Issue: 3
Author(s): Lakshmanan Loganathan, S. Justin Carlus and Karthikeyan Muthusamy*
Affiliation:
- Pharmacogenomics and CADD Laboratory, Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu,India
Keywords:
Molecular docking, molecular dynamics, NS3 helicase, DFT theory, drug repurposing, natural drugs, zika virus.
Abstract: Background: Ancestral recapitulation of the Zika virus from Uganda, Africa, an epidemic
in American territories since 2015, was reported by CDC, 2016. To date, there is no specific vaccine
or drug for the Zika virus.
Objective: The study aims to identify the potential inhibitors that have the capability to be effective
against Zika virus. Natural and FDA-approved anti-viral drug molecules are utilized through the drug
repurposing approach to screen the lead compounds.
Methods: Molecular docking approach was utilized to screen the best hit compounds. The identified
compounds were further evaluated through binding free energy calculations and physiochemical
properties. Density functional theory calculations were calculated for the best hit compounds to observe
the structural properties and electrophilic/nucleophilic attack at the quantum level. Furthermore,
molecular dynamic simulation studies provide insight into structural stability and conformational
analysis of the protein and ligand molecules.
Result: Non-covalent interactions observed between the molecules are Gly199, Lys200, Thr201,
Arg202, Asn417, Glu231, Glu286, and Arg459. Telaprevir, a Hepatitis C virus (NS3/4 protease)
inhibitor, and Curcuma Longa, a natural drug, are found to be more potent druggable candidates
among the screened leads for the Zika virus.
Conclusion: The results of the study suggest Telaprevir and Curcuma Longa to be considered as the
lead agents for experimental studies on Zika virus. The outcome of the study may provide much
knowledge in designing anti-zika drugs in the future.
