In-silico study of peptide-protein interaction of antimicrobial peptides potentially targeting SARS and SARS-CoV-2 nucleocapsid protein.

This study is an attempt to find a suitable therapy using antimicrobial peptides (AMPs) by identifying peptide-protein interaction of AMPs and nucleocapsid protein of SARS and SARS-CoV- 2. The AMPs were shortlisted from the APD3 database (Antimicrobial peptide database) based on various physicochemical parameters. The binding efficacy of AMPs was measured using the lowest energy score of the docked complexes with 10 selected AMPs. For SARS-CoV, AP00180 showed the best pose with a binding affinity value of - 6.4 kcal/mol. Prominent hydrogen bonding interactions were observed between Lys85 (nucleocapsid receptor) and Arg13 (antimicrobial peptide ligand) having the least intermolecular distance of 1.759 Å. For SARS-CoV-2, AP00549 was docked with a binding affinity value of - 3.4 kcal/mol and Arg119 and Glu14 of receptor nucleocapsid protein and ligand AMP having the least intermolecular distance of 2.104 The dynamic simulation was performed at 50 ns to check the stability of the final docked complexes, one with each protein. The two best AMPs were AP00180 (Human Defensin-5) for SARS and AP00549 (Plectasin) for SARS-CoV-2. From positive results of dynamic simulation and previously known knowledge that some AMPs interact with the nucleocapsid of coronaviruses, these AMPs might be used as a potential therapeutic agent for the treatment regime of SARS-CoV-2 and SARS infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00103-z.

In silico screening of potential lead compounds against 3-oxo-5-alpha-steroid 4-dehydrogenase 2 for treating prostate cancer.

Increased levels of androgen dihydrotestosterone is responsible for the development of prostate cancer in humans. The formation of dihydrotestosterone from testosterone is catalysed by an intracellular enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase 2, which is found to be the most promising target for the treatment of prostate cancer. In this study, the identification of a therapeutic inhibitor of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 using in silico approach has been done to treat prostate cancer. ZINC biogenic compounds (Zbc) database was used for docking and virtual screening against the predicted structure. The MD simulation of the docked complex was done to ensure the ligand interaction with 3-oxo-5-alpha-steroid 4-dehydrogenase 2 for 100 ns. The validation results of the established 3D structure strongly favoured the acceptance reliability of the predicted model. Zbc was screened against 3-oxo-5-alpha-steroid 4-dehydrogenase 2 and ZINC00277963 was selected as the lead with significant docking pose with docking score of -9.961 kcal/mole and having -63.182 kcal/mol binding affinity. The protein-ligand complex system remained stable throughout the MD run and seven stable hydrogen bonds were observed. Our study proposes a lead compound that could be validated by in vitro experimental method(s), suggesting its ability to function as a prospective therapeutic drug against prostate cancer.