A computational multi-targeting approach for drug repositioning for psoriasis treatment

Abstract

Abstract Background Psoriasis is an autoimmune inflammatory skin disease that affects 0.5–3% of the world’s population and current treatment options are posed with limitations. The reduced risk of failure in clinical trials for repositioned drug candidates and the time and cost-effectiveness has popularized drug reposition and computational methods in the drug research community. Results The current study attempts to reposition approved drugs for the treatment of psoriasis by docking about 2000 approved drug molecules against fifteen selected and validated anti-psoriatic targets. The docking results showed that a good number of the dataset interacted favorably with the targets as most of them had − 11.00 to − 10.00 kcal/mol binding free energies across the targets. The percentage of the dataset with binding affinity higher than the co-crystallized ligands ranged from 34.76% (JAK-3) to 0.73% (Rac-1). It was observed that 12 out of the 0.73% outperformed all the co-crystallized ligands across the 15 studied proteins. All the 12 drugs identified are currently indicated as either antiviral or anticancer drugs and are of purine and pyrimidine nuclei. This is not surprising given that there is similarity in the mechanism of the mentioned diseases. Conclusion This study, therefore, suggests that; antiviral and anticancer drugs could have anti-psoriatic effects, and molecules with purine and pyrimidine structural architecture are likely templates to consider in developing anti-psoriatic agents.

Keywords

• Binding free energies
• Docking
• Drug repositioning
• Psoriasis