Potential inhibitory activity of phytoconstituents against black fungus: in silico admet, molecular docking and MD simulation studies

Mucormycosis or “black fungus” has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions

HOMOLOGY MODELING OF MTNR1B AND INSILICO STRUCTURE ACTIVITY RELATIONSHIP STUDY OF MELATONIN ANALOGS FOR THERAPEUTIC APPLICATION IN INSOMNIA AND INSOMNIA RELATED DIABETES.

Melatonin is a circulating hormone that is primarily released from the pineal gland and performs a circadian rhythm in human and plays a vital role in insomnia and diabetes. In order to search promising MTNR1B homolog inhibitors, an in-silico study is carried out. Since there is no reported MTNR1B crystal structural data, three dimensional structure of MTNR1B was modeled based on crystal structure of the Mos1 mariner (PDB: 3HOT_A) and validated using PROCHECK, Ramchandran plot and energy optimization techniques. Further implementing the Insilico molecular modeling and interaction study approaches were performed with 6 different inhibitors including melatonin and reference molecule as a Ramelteon with 5 different cavities detected by MVD where Cavity 2 resulted to a least and favorable energy among all. Melatonin with acetyl side chain extended with butyryl which followed Lipinski rule of five, and a combinatorial library of 177 analogs are designed. After several docking study and Lipinski screening, successively 3 melatonin analogs are designed and screened, which may have a better therapeutic application to the melatonin