Virtual screening of plant phytochemicals to discover potent Janus kinase-1 inhibitors against severe COVID-19 and sepsis
by Kavita Joshi; Shradheya R.R. Gupta; Shubham Verma; Rakesh Sharma; Sameer Qureshi; Mansoor Ali Syed; Vandana Nunia
International Journal of Computational Biology and Drug Design (IJCBDD), Vol. 15, No. 5, 2023

Abstract: Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals and play a major role in the progression of multiple organ dysfunction syndrome (MODS) caused by sepsis and virus-induced SARSCOVID-19. In this study, we focused on finding the potential phytochemicals to inhibit JAK1. We prepared and screened a library of 5229 diverse phytochemicals and filtered out 2081 compound based on drug likeness properties. These compounds were docked with the JAK1 kinase domain with Upadacitinib, (a FDA approved JAK-1 inhibitor) used as reference. We have further shortlist the compounds based on their docking binding energy, which was higher than that Upadacitinib. The top four compounds Kudzuisoflavone B, Taiwaniaflavone 7-O-methyl ether, Formosanatin D, and Withaphysalin A, showed binding energy -12 Kcal/mol, were further subjected to dynamic simulation. Based on the RMSD, RMSF, H-bond, hydrophobic interactions, MMPBSA and GROMACS total energy, Kudzuisoflavone B was selected as potent Jak-1 inhibitor among all compounds.

Online publication date: Wed, 04-Oct-2023

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