Virtual screening indicates potential inhibitors of the P2X7 receptor

by Selleckchem | Nov 14 2023

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.

Comments:

The passage you provided discusses the importance of identifying anti-inflammatory agents, both synthetic and natural, for the treatment of inflammatory diseases. It highlights that inflammatory diseases can be challenging to treat due to their involvement in multiple systems, the need for long-term therapy, high treatment costs, and their impact on public health. As a result, researchers are actively searching for compounds with anti-inflammatory properties, and this search involves both synthetic drugs and natural products.

The passage also mentions a specific study involving the virtual screening of 2774 molecules on the mouse P2X7 protein. This screening identified potential ligands, including five flavonoids (narirutin, diosmin, complanatuside, hesperidin, and oroxin B), as well as other drugs like velpatasvir, itacitinib, and lifitegrast. In vitro studies were conducted in mouse cells to confirm the inhibitory activity of these ligands on the P2X7 receptor.

Furthermore, the behavior of the protein bonded to these ligands was assessed through molecular dynamic simulations for four of the most potent inhibitor compounds: velpatasvir, itacitinib, lithospermic acid, and narirutin. The simulations indicated that these ligands remained in the binding site, as suggested by molecular docking.

In summary, this passage underscores the importance of identifying anti-inflammatory compounds, both natural and synthetic, through virtual screening and in vitro studies. It also mentions specific compounds that have shown potential as inhibitors of the P2X7 receptor, which plays a role in inflammation. Molecular dynamic simulations were used to understand the behavior of these compounds when bound to the receptor.