Phytochemical Analysis, In Vitro Biological Activities, and Computer-Aided Analysis of Potentilla nepalensis Hook Compounds as Potential Melanoma Inhibitors Based on Molecular Docking, MD Simulations, and ADMET.

Potentilla nepalensis Hook is a perennial Himalayan medicinal herb of the Rosaceae family. The present study aimed to evaluate biological activities such as the antioxidant, antibacterial, and anticancer activities of roots and shoots of P. nepalensis and its synergistic antibacterial activity with antibacterial drugs. Folin-Ciocalteau and aluminium chloride methods were used for the calculation of total phenolic (TPC) and flavonoid content (TFC). A DPPH radical scavenging assay and broth dilution method were used for the determination of the antioxidant and antibacterial activity of the root and shoot extracts of P. nepalensis. Cytotoxic activity was determined using a colorimetric MTT assay. Further, phytochemical characterization of the root and shoot extracts was performed using the Gas chromatography-mass spectrophotometry (GC-MS) method. The TPC and TFC were found to be higher in the methanolic root extract of P. nepalensis. The methanolic shoot extract of P. nepalensis showed good antioxidant activity, while then-hexane root extract of P. nepalensis showed strong cytotoxic activity against tested SK-MEL-28 cells. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer properties. This study can lead to the production of new herbal medicines for various diseases employing P. nepalensis, leading to the creation of new medications.

Repurposing of anticancer phytochemicals for identifying potential fusion inhibitor for SARS-CoV-2 using molecular docking and molecular dynamics (MD) simulations.

The viral particle, SARS-CoV-2 is responsible for causing the epidemic of Coronavirus disease 2019 (COVID-19). To combat this situation, numerous strategies are being thought for either creating its antidote, vaccine, or agents that can prevent its infection. For enabling research on these strategies, several target proteins are identified where, Spike (S) protein is of great potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for entering the cell. S-protein is a large protein and a portion of it designated as a receptor-binding domain (RBD) is the key region that interacts with ACE2, following to which the viral membrane fuses with the alveolar membrane to enter the human cell. The hypothesis is to identify molecules from the pool of anticancer phytochemicals as a lead possessing the ability to interact and mask the amino acids of RBD, making them unavailable to form associations with ACE2. Such a molecule is termed as 'fusion inhibitor'. We hypothesized to identify fusion inhibitors from the NPACT library of anticancer phytochemicals. For this, all the molecules from the NPACT were screened using molecular docking, the five top hits (Theaflavin, Ginkgetin, Ursolic acid, Silymarin and Spirosolane) were analyzed for essential Pharmacophore features and their ADMET profiles were studied following to which the best two hits were further analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals containing anticancer properties to serve as fusion inhibitors.Communicated by Ramaswamy H. Sarma.