Potential peptidyl arginine deiminase type 4 inhibitors from Morinda citrifolia: a structure-based drug design approach.

The World Health Organization estimates that more than 23 million individuals worldwide suffer from rheumatoid arthritis (RA), a chronic systemic autoimmune disease and experts predict that the number of RA patients may double by 2030. A substantial portion of RA patients do not respond effectively to the treatment that are already available therefore there is an urgent need of innovative new drugs. Over the past several years, Peptidyl Arginine Deiminase Type 4 (PAD4) receptors have become potential therapeutic targets for the treatment of RA. The main objective of the present study is to identify potential PAD4 inhibitors from edible fruits Morinda citrifolia. Structure based virtual screening (VS) of 60 compounds from M. citrifolia were performed to identify PAD4 inhibitors. The virtual screening of compounds resulted ten hits having XP-Glide score greater than the co-ligand (XPGS: - 8.341 kcal/mol). Three hits NF_15, NF_34, and NF_35 exhibited admirable MM-GBSA dG binding energy - 52.577, - 46.777, and - 60.711 kcal/mol, respectively. These three compounds were chosen for 100 ns molecular dynamics (MD) simulations in order to evaluate the stability and interactions. The protein-ligand complex with the highest level of stability was revealed to be NF_35. Therefore, M. citrifolia fruits may be beneficial in the treatment and prevention of rheumatoid arthritis since it contains potential hits.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-023-00147-3.