Computational Screening and Cytotoxic Analysis of Beta vulgaris L. phytoconstituents as potent Dengue virus-NS5 Polymerase inhibitors.

Dengue infection is one of the most widely spread flavivirus infections. Despite the fatality it could cause, no antiviral treatment is currently available to treat the disease and its associated pathophysiological conditions. This study aimed to search drug-like compounds for possible inhibitors of the NS5 protein of dengue virus (serotype 2). In the present study, a data set of twenty-five Beta vulgaris. L-based phytoconstituents was developed. We employed machine learning (ML) data pre-processing, screening of differentially expressed transcripts and genes, identification of common transcriptional signatures and pathways and function enrichment analysis of dengue infection; and protein-protein interaction network construction and identification of hub genes. ML data revealed that NS5 mRNA was downregulated by betanin, kaempferol, quercetin hydrate, and isovitexin-2-O-xyloside. Moreover, administering these compounds can alleviate host innate immune factor suppression mediated by NS5, thereby exhibiting antiviral activity. Molecular docking and pharmacokinetics studies revealed a potential therapeutic role of betanin, kaempferol, quercetin hydrate, and isovitexin-2-O-xyloside phytoconstituents as potent antiviral phytocompounds. MD simulation and post-simulation analysis, including principal component analysis and dynamic cross-correlation, confirmed the antiviral therapeutic potency of betanin, kaempferol, and isovitexin-2-O-xyloside against dengue virus infection. In vitro cytotoxic studies also depicted nontoxic effects of betanin and quercetin hydrate in Vero and CHO cells at a concentration range of 20-0.31 μM. In summary, computational screening and in vitro cytotoxicity analysis revealed that betanin, kaempferol, and isovitexin-2-O-xyloside may prove as potential drug candidates against dengue virus regarding their possible safety and antiviral activity in future.