Inhibitory effect of lupeol, quercetin, and solasodine on Rhizopus oryzae: A molecular docking and dynamic simulation study.

BACKGROUND: Mucormycosis is an infection caused by fungi belonging to the order Mucorales. Rhizopus oryzae is one of the most prevalent organisms identified in mucormycosis patients. Because it spreads quickly through the blood vessels, this opportunistic illness has an exceptionally high fatality rate, even when vigorous treatment is administered. Nonetheless, it has a high tolerance to antifungal medicines, limiting treatment options. As a result, improved methods for preventing and treating mucormycosis are desperately needed. Hence, this study was aimed at assessing the effect of lupeol, quercetin, and solasodine against mucormycosis based on computational approaches. METHODS: The Rhizopus oryzae RNA-dependent RNA polymerase (RdRp) was the target for the design of drugs against the deadly mucormycosis. The three-dimensional structure of the RdRp was modelled with a Swiss model and validated using PROCHECK, VERIFY 3D, and QMEAN. Using the Schrodinger maestro module, a molecular docking study was performed between RdRp and the antimicrobial phytochemicals lupeol, quercetin, and solasodine. A molecular dynamics (MD) simulation study was used to assess the stability and interaction of the RdRp with these phytochemicals. RESULTS: The RdRp protein binds strongly to lupeol (-7.2 kcal/mol), quercetin (-9.1 kcal/mol), and solasodine (-9.6 kcal/mol), according to molecular docking assessment based on the lowest binding energy, confirmation, and bond interaction. Simulations suggest that lupeol, quercetin, and solasodine complexes with RdRp and showed stable confirmation with minimal fluctuation throughout the 200 nanoseconds based on the RMSD and RMSF trajectory assessments. CONCLUSION: The molecular docking and MD simulation investigation improved our understanding of phytochemical-RdRp interactions. Due to its high affinity for RdRp, solasodine may be a better treatment option for mucormycosis.

Prenatal exposure to bisphenol-A altered miRNA-224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F1 adult offspring.

This study was aimed to predict bisphenol-A (BPA)-responsive miRNA's using an in silico approach and to study their expression in granulosa cells of animals exposed prenatally to BPA. Pregnant Wistar rats were exposed to BPA through water (25 µg/L, 250 µg/L, and 2.5 mg/L) during gestation. The expression of miRNA-133b, miRNA-378 and miRNA-224 were analyzed in ovarian granulosa cells. BPA affected the postnatal developmental landmarks such as weight of the pups at birth and reduced anogenital distance. BPA exposed animals showed elevated serum estradiol (E2) levels, while follicle-stimulating hormone levels were reduced. The expression of miRNA-224 and aromatase protein levels were found to be increased. This preliminary finding reveals the impact of early life exposure to BPA on the long-term ovarian functions that may be mediated through miRNA-based granulosa cell response. Besides, it is also a compelling indicator for the subclinical response that could have important consequences on female fertility.