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Pharmacoinformatics-based screening of active compounds from Vitex negundo against lymphatic filariasis by targeting asparaginyl-tRNA synthetase

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Abstract

Context

Lymphatic filariasis, generally called as elephantiasis, is a vector-borne infectious disease caused by the filarial nematodes, mainly Wuchereria bancrofti, Brugia malayi, and Brugia timori, which are transmitted through mosquitoes. The infection affects the normal flow of lymph leading to abnormal enlargement of body parts, severe pain, permanent disability, and social stigma. Due to the development of resistance as well as toxic effects, existing medicines for lymphatic filariasis are becoming ineffective in killing the adult worms. It is essential to search novel filaricidal drugs with new molecular targets. Asparaginyl-tRNA synthetase (PDB ID: 2XGT) belongs to the group of aminoacyl-tRNA synthetases that catalyze specific attachment of amino acids to their tRNA during protein biosynthesis. Plants and their extracts are well-known medicinal practice for the management of several parasitic infectious diseases including filarial infections.

Methods

In this study, asparaginyl-tRNA synthetase of Brugia malayi was used as a target to perform virtual screening of plant phytoconstituents of Vitex negundo from IMPPAT database, which exhibits anti-filarial and anti-helminthic properties. A total of sixty-eight compounds from Vitex negundo were docked against asparaginyl-tRNA synthetase using Autodock module of PyRx tool. Among the 68 compounds screened, 3 compounds, negundoside, myricetin, and nishindaside, exhibited a higher binding affinity compared to standard drugs. The pharmacokinetic and physicochemical prediction, stability of ligand-receptor complexes via molecular dynamics simulation, and density functionality theory were done further for the top-scored ligands with receptor.

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Data availability

Not applicable.

Code availability

This work was conducted using the free software Autodock Vina module in PyRx 0.8 software and GROMACS.

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Acknowledgements

The authors acknowledge the Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamil Nadu, India, for providing essential facilities to perform the research work, and Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bengaluru, for providing computational facility for research work.

Funding

Funding acquisition from Department of Biotechnology, Kalasalingam Academy of Research and Education, India.

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Authors and Affiliations

  1. Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, 626126, Tamil Nadu, India

    Shanmugampillai Jeyarajaguru Kabilan, Selvaraj Kunjiappan, Krishnan Sundar, Nivethitha Sathishkumar & Haritha Velayuthaperumal

  2. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru, 560054, Karnataka, India

    Parasuraman Pavadai

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  1. Shanmugampillai Jeyarajaguru Kabilan
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Contributions

Shanmugampillai Jeyarajaguru Kabilan: conceptualization, reviewing and editing, resources, and supervision.

Selvaraj Kunjiappan: simulations, data collection, analysis, and writing—original draft preparation.

Krishnan Sundar: reviewing and editing, resources, and formal analysis.

Parasuraman Pavadai: simulations, data collection, analysis, and writing—original draft preparation.

Nivethitha Sathishkumar: material preparation, data collection, analysis, and writing—original draft preparation.

Haritha Velayuthaperumal: material preparation, data collection, analysis, and writing—original draft preparation.

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Correspondence to Shanmugampillai Jeyarajaguru Kabilan.

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Kabilan, S.J., Kunjiappan, S., Sundar, K. et al. Pharmacoinformatics-based screening of active compounds from Vitex negundo against lymphatic filariasis by targeting asparaginyl-tRNA synthetase. J Mol Model 29, 87 (2023). https://doi.org/10.1007/s00894-023-05488-6

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