A Sphingolipidomic Profiling Approach for Comparing X-ray-Exposed and Unexposed HepG2 Cells.

An analytical method based on tandem mass spectrometry-shotgun is presently proposed to obtain sphingolipidomic profiles useful for the characterization of lipid extract from X-ray-exposed and unexposed hepatocellular carcinoma cells (HepG2). To obtain a targeted lipidic profile from a specific biological system, the best extraction method must be identified before instrumental analysis. Accordingly, four different classic lipid extraction protocols were compared in terms of efficiency, specificity, and reproducibility. The performance of each procedure was evaluated using the Fourier-transform infrared spectroscopic technique; subsequently, the quality of extracts was estimated using electrospray ionization tandem mass spectrometry. The selected procedure based on chloroform/methanol/water was successfully used in mass spectrometry-based shotgun sphingolipidomics, allowing for evaluation of the response of cells to X-ray irradiation, the most common anticancer therapy. Using a relative quantitative approach, the changes in the sphingolipid profiles of irradiated cell extracts were demonstrated, confirming that lipidomic technologies are also useful tools for studying the key sphingolipid role in regulating cancer growth during radiotherapy.

Anthocyanin derivatives as potent inhibitors of SARS-CoV-2 main protease: An in-silico perspective of therapeutic targets against COVID-19 pandemic.

A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To treat the patients with coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds based natural products targeting main protease (Mpro) enzyme of SARS-CoV-2. The Mpro enzyme plays a key role in mediating viral replication and transcription and thus being considered as an attractive drug target. Herein, comprehensive computational investigations were performed to identify new lead compounds against main protease enzyme. In this study, the candidate anthocyanin-derived compounds from PubChem database were filtered considering antiviral characteristics of anthocyanins. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening-based PHASE Screen Score. Docking based virtual screening work flow was used to generate hit compounds using HTVS, SP and XP based Glide Gscore. The obtained hit compounds were filtered using ADMET pharmacological and physicochemical properties screening. Molecular dynamics simulations were performed to explore the binding affinities of the considered compounds. Our study identified six best anthocyanin-derived natural compounds which could be used as promising lead compounds against main protease SARS-CoV-2 virus.