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Ethyl 4-(4-methylphenyl)-4-pentenoate from Vetiveria zizanioides Inhibits Dengue NS2B–NS3 Protease and Prevents Viral Assembly: A Computational Molecular Dynamics and Docking Study

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Abstract

Around 50 % of the world’s population is at the risk of dengue, a viral infection. Presently, there are not many drugs and prophylactic measures available to control dengue viral infection, and hence, there is an urgent need to develop effective antidengue compound from natural sources. In the current study, we explored the antiviral properties of the medicinal plant Vetiveria zizanioides against dengue virus. Initially, the antiviral properties of active compounds were examined using docking analysis along with reference ligand. The enzyme–ligand complex which showed higher binding affinity than the reference ligand was employed for subsequent analysis. The stability of the top scoring enzyme–ligand complex was further validated using molecular simulation studies. On the whole, the study reveals that the compound Ethyl 4-(4-methylphenyl)-4-pentenoate has an effective antiviral property, which can serve as a potential lead molecule in drug discovery process.

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Abbreviations

ADMET:

Absorption, distribution, metabolism, excretion, and toxicity

CDC:

Centre for Disease Control and Prevention

DENV:

Dengue virus

LINCS:

Linear constraint solver

MOLCAD:

Molecular computer-aided design

NS:

Nonstructural

NVT:

Constant number of particles, volume, and temperature

NPT:

Constant number of particles, pressure, and temperature

PDB:

Protein data bank

PME:

Particle mesh Ewald

RMSD:

Root mean square deviation

RMSF:

Rood mean square fluctuation

Vetiveria zizanioides :

V. zizanioides

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Acknowledgments

Dr. Anand Anbarasu and Dr. Sudha Ramaiah gratefully acknowledge the Indian Council of Medical Research (ICMR), Government of India Agency for the research grant [IRIS ID: 2014-0099]. P. Lavanya thanks ICMR for the Research fellowship. We would like to thank the management of VIT University for providing us the necessary facilities to carry out this research project.

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Authors and Affiliations

  1. Medical & Biological Computing Laboratory, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India

    P. Lavanya, Sudha Ramaiah & Anand Anbarasu

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  1. P. Lavanya
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  2. Sudha Ramaiah
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Correspondence to Anand Anbarasu.

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Lavanya, P., Ramaiah, S. & Anbarasu, A. Ethyl 4-(4-methylphenyl)-4-pentenoate from Vetiveria zizanioides Inhibits Dengue NS2B–NS3 Protease and Prevents Viral Assembly: A Computational Molecular Dynamics and Docking Study. Cell Biochem Biophys 74, 337–351 (2016). https://doi.org/10.1007/s12013-016-0741-x

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