Virtual screening indicates potential inhibitors of the P2X7 receptor.

Anti-inflammatory agents can be synthetic or natural compounds and are often used to attenuate different levels of inflammation. Inflammatory diseases, due to the involvement of multiple systems, are becoming difficult to treat, involve long durations of therapy where applicable, have a high cost of management and have a deleterious impact on public health. The search for natural and synthetic compounds with anti-inflammatory activity is an important strategy in drug design. Bioactive synthetic drugs may be repurposed for other pharmacological applications, and natural product chemical structures offer unlimited opportunities for new drug discoveries due to the unparalleled availability of chemical diversity. Virtual screening of 2774 molecules on the mouse P2X7 protein showed that potential ligands are composed of five flavonoids (narirutin, diosmin, complanatuside, hesperidin, and oroxin B) and other drugs such as velpatasvir, itacitinib and lifitegrast. In vitro studies in mouse cells confirmed the inhibitory activity of the indicated ligands on the P2X7 receptor by applying virtual screening. The behavior of protein bonded to the ligands was verified by analysis of the molecular dynamic simulation trajectories for four of the most potent inhibitor compounds, indicating that the ligands velpatasvir, itacitinib, lithospermic acid and narirutin remained in the binding site indicated by molecular docking.