<i>In Silico</i> Analysis of Drug Repurposing Strategy for the Identification of Potential NS3 Helicase Inhibitors Against Zika Virus

Author(s):

Lakshmanan Loganathan, S. Justin Carlus and Karthikeyan Muthusamy*   Pages 373 - 385 ( 13 )

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. </p> 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. </p> 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. </p> 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. </p> 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.

Keywords:

Molecular docking, molecular dynamics, NS3 helicase, DFT theory, drug repurposing, natural drugs, zika virus.

Affiliation:

Pharmacogenomics and CADD Laboratory, Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu, Molecular Genetics Laboratory, Rainbow Children’s Hospital, Banjara Hills, Hyderabad, Telangana, Pharmacogenomics and CADD Laboratory, Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu

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