Prediction of binding potential of natural leads against the prioritized drug targets of chikungunya and dengue viruses by computational screening

摘要

The current study aimed to assess the binding potential of herbal lead molecules against the prioritized molecular targets of chikungunya virus (CHIKV) and dengue virus (DENV) by computational virtual screening and suggests a novel therapeutic intervention. Based on the metabolic pathway analysis and virulent functions, the non-structural and envelop proteins present in CHIKV and DENV were identified as putative drug targets. The structures of the protein not available in their native forms were computationally predicted by homology modeling. The lead compounds from 43 herbal sources were screened and their drug likeliness and pharmacokinetics properties were computationally predicted. The binding potential of selected phytoligands against the prioritized drug targets were analyzed by molecular docking studies. This study revealed that Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one) and Chymopain (disodium;4,5-dihydroxybenzene-1,3-disulfonate), natural flavonols present in Carica papaya and Gossypetin (3, 5, 7, 8, 3′, 4′-hexahydroxyflavone), a natural flavonoid available in Hibiscus sabdariffa were demonstrated promising good binding potential with minimum binding energy (kcal/mol) and maximum stabilizing interactions to the putative drug targets of CHIKV and DENV. The selected lead molecules demonstrated ideal drug likeliness, ADMET (adsorption, distribution, excretion, metabolism and toxicity) features required for the drug development. The molecular docking studies suggested that the presence of these compounds probably responsible for the antiviral properties of Carica papaya, which was traditionally known as therapeutic remedy for dengue viral infections. This study provides profound insight for the experimental validation of the applied approach and industrial scale-up of the suggested herbal lead molecules as promising lead candidates against CHIKV and DENV infections.Electronic supplementary materialThe online version of this article (10.1007/s13205-018-1303-2) contains supplementary material, which is available to authorized users.