In Vitro and In Vivo Antibiofilm Potential of Eicosane Against Candida albicans.

Candida albicans is the most prevalent fungus in humans, producing infections ranging from mucosal to systemic. C. albicans colonizes mucosal surfaces asymptomatically as commensal, but, if the host environment is disrupted, or if the host immune system is compromised, C. albicans can multiply and infect almost all places in the host. The present study was aimed to identify a promising antibiofilm agent against Candida albicans biofilm. Through the molecular docking approach, it was identified that Eicosane was the top hit among the alkanes screened. Furthermore, in vitro analysis revealed that Eicosane at 100 µg/mL was able to inhibit 60% of C. albicans biofilm without inhibiting the growth. Moreover, light microscopic investigation unveiled the significant reduction in the adhesion and colonization of yeast cells to the matrix on Eicosane-treated samples. The CLSM images showing a reduction in biomass and thickness of C. albicans biofilm in the presence of Eicosane were validated using COMSTAT. The results were well corroborated with SEM micrograph in which a pellucid gap between the cells was observed and colonization was considerably reduced. Further from qPCR analysis, the genes responsible for biofilm formation and hyphal growth were found to be downregulated in the presence of Eicosane. Similarly, Eicosane at BIC was able to significantly inhibit the adhesion and colonization of yeast cells on the chorion of the zebrafish embryos. Moreover, the binding ability of Eicosane to ALS3 was revealed through docking and molecular dynamics (MD) simulation studies.

Ethnomedicines of Indian origin for combating COVID-19 infection by hampering the viral replication: using structure-based drug discovery approach.

In the present study, we have explored the interaction of the active components from 10 different medicinal plants of Indian origin that are commonly used for treating cold and respiratory-related disorders, through molecular docking analysis. In the current scenario, COVID-19 patients experience severe respiratory syndromes, hence it is envisaged from our study that these traditional medicines are very likely to provide a favourable effect on COVID-19 infections. The active ingredients identified from these natural products are previously reported for antiviral activities against large group of viruses. Totally 47 bioactives identified from the medicinal plants were investigated against the structural targets of SARS-CoV-2 (Mpro and spike protein) and human ACE2 receptor. The top leads were identified based on interaction energies, number of hydrogen bond and other parameters that explain their potency to inhibit SARS-CoV-2. The bioactive ligands such as Cucurbitacin E, Orientin, Bis-andrographolide, Cucurbitacin B, Isocucurbitacin B, Vitexin, Berberine, Bryonolic acid, Piperine and Magnoflorine targeted the hotspot residues of SARS-CoV-2 main protease. In fact, this protease enzyme has an essential role in mediating the viral replication and therefore compounds targeting this key enzyme are expected to block the viral replication and transcription. The top scoring conformations identified through docking analysis were further demonstrated with molecular dynamics simulation. Besides, the stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Overall, the study emphasized that the proposed hit Cucurbitacin E and orientin could serve as a promising scaffold for developing anti-COVID-19 drug.Communicated by Ramaswamy H. Sarma.