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

• Published in: Journal of molecular modeling 2023-04, Vol.29 (4), p.87-87, Article 87
• Main Authors: Kabilan, Shanmugampillai Jeyarajaguru, Kunjiappan, Selvaraj, Sundar, Krishnan, Pavadai, Parasuraman, Sathishkumar, Nivethitha, Velayuthaperumal, Haritha
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Aspartate-tRNA Ligase; Biosynthesis; Body parts; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Drugs; Dynamic stability; Elephantiasis, Filarial; Infectious diseases; Ligands; Molecular dynamics; Molecular Medicine; Nematodes; Original Paper; Parasitic diseases; Pharmacology; Receptors; RNA, Transfer, Amino Acyl; Screening; Theoretical and Computational Chemistry; Transfer RNA; Tropical diseases; Vitex
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-023-05488-6

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.