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

Akachukwu Ibezim,Fidele Ntie-Kang,Emmanuel Onah,Ebubechukwu N Dim

doi:10.1186/s12906-021-03359-2

Abstract

BackgroundPsoriasis 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.ResultsThe 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.ConclusionThis 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.

Highlights

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 field of drug repositioning is growing rapidly because it starts from compounds, which are often Food and Drug Administration (FDA) approved drugs, with well-characterized
In our previous investigation of the medicinal plant, Psorospermum febrifugum Spach, we provided evidence that confirm its ethnopharmacological usage as antipsoriatic agent and further identified forty-two fatty acids from the GC-MS chromatogram of the most active extract fraction which could be responsible for its biological activity [24]

Summary

Introduction

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. Psoriasis is an autoimmune inflammatory skin disease that affects 0.5–3% of the world’s population [1] It is caused by the complex interplay of the innate and adaptive immune systems together with a wide array of genetic and environmental factors. Environmental triggers such as stress, injury, drugs, and the disease start the self-propelled cycle of inflammation culminating in. Ibezim et al BMC Complementary Medicine and Therapies (2021) 21:193 pharmacology and safety profiles Benefits accompanying this strategy are reduction in the risk of attrition in drug development during clinical trials and subsequently cost [12, 13]. When compared with diseases like cancer where previously known drugs have been repurposed, e.g. the painkiller aspirin for cancer prevention, metformin previously known for the treatment of type-2 diabetes to protect against cancer development [16, 17], no repurposed drug has been established as a treatment for psoriasis to date, suggesting the current study

Methods

Results

Conclusion