Carbonic anhydrase IX (hCAIX) is a membrane-spanning metalloenzyme, encoded by CA9 gene, which can lead to various carcinomas if upregulated. Due to its overexpression in many cancer tissues, hCAIX has become a promising target for developing anticancer therapeutics. Furthermore, several classes of small-molecules have shown to inhibit the hCAIX expression. In this study, therefore, we screened (n = 42) plant-derived compounds to identify the most potent hCAIX inhibitors and to understand their interactions with hCAIX and drug candidacy through in silico approaches. Among all, only 3 compounds (i.e., fraxoside, scopolin, and xanthone,) provided higher binding affinity towards hCAIX protein as compared to the native ligand. In standard docking, scopolin showed -4.97 kcal/mol of binding energy with hCAIX while control ligand provided -4.45 kcal/mol. In precise docking, the highest binding affinity was found for fraxoside (-7.67 kcal/mol) as compared to -3.04 kcal/mol of the control. The Gibbs free energy (ΔG) of these potent leads was also consistent and in support of the docking studies. The binding interactions were also found to be stable in dynamics simulation. Furthermore, analysis of protein-protein interactions and co-expression revealed the possible association of CA9 gene with other tumorous genes, especially angiogenesis factor HIF1A which will most likely be affected by the identified inhibitors. With further experimental validation, therefore, these potential inhibitors could be effective against hCAIX protein, thereby, paving the way for prospective anticancer therapeutics.

Ralstonia solanacearum is a harmful pathogen that causes severe wilt disease in several vegetables. In the present study, we identified R. solanacearum from wilt of papaya by 16S rRNA PCR amplification. Virulence ability of R. solanacearum was determined by amplification of approximately 1500 bp clear band of hrpB gene. Further, in-vitro seed germination assay showed that R. solanacearum reduced the germination rate up to 26.21%, 34% and 33.63% of cucumber, bottle guard and pumpkin seeds, respectively whereas shoot and root growth were also significantly decreased. Moreover, growth inhibition of R. solanacearum was recorded using antibacterial compound from medicinal plant and antagonistic B. subtilis. Petroleum ether root extract of Rauvolfia serpentina showed highest 22 ± 0.04 mm diameter of zone of inhibition where methanolic extract of Cymbopogon citratus and ethanolic extract of Lantana camara exhibited 20 ± 0.06 mm and 20 ± 0.01 mm zone of inhibition against R. solanacearum, respectively. In addition, bioactive compounds of B. subtilis inhibited R. solanacearum growth by generating 17 ± 0.09 mm zone of inhibition. To unveil the inhibition mechanism, we adopted chemical-protein interaction network and molecular docking approaches where we found that, rutin from C. citratus interacts with citrate (Si)-synthase and dihydrolipoyl dehydrogenase of R. solanacearum with binding affinity of −9.7 kcal/mol and −9.5 kcal/mol while quercetin from B. subtillis interacts with the essential protein F0F1 ATP synthase subunit alpha of the R. solancearum with binding affinity of −6.9 kcal/mol and inhibit the growth of R. solanacearum. Our study will give shed light on the development of eco-friendly biological control of wilt disease of papaya.