Identification of new inhibitors of the toxoplasma gondii by using in-silico drug repurposing

Abstract

Introduction:The common treatment for toxoplasmosis was pyrimethamine. In recent years, it has been found that this parasite is getting resistant to this treatment, therefore urgent alternative treatments are needed. Material and Methods: In this study, by using drug repurposing and in silico methods we tried to make a selective treatment by inhibiting the Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii which doesn't exist in mammalians. We screened the FDA approved drugs by molecular docking and after ranking them by their binding energies and inspecting the top scored ones, we chose Cefpiramide, Ceftriaxone and Cefotiam as the hit compounds. After that, we used molecular dynamics simulations to test the hit compounds in a much more realistic environment. Results: By analyzing the results, we found that all of the hit compounds and good and can bind strongly to the active site of the protein. Therefore, they can be potential candidates for inhibiting Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii. Conclusion: Moreover, because the predicted compounds are FDA approved drugs, their toxicity profiles are well known and their newly predicted use can be tested in clinical trials.

Cytotoxic and Immunomodulatory Activity of Curcumin and Chitosan on Experimental Toxoplasmosis

“…Therefore, it could be a potential candidate for inhibiting Toxoplasma gondii viability. In a similar study ( 10 ), using a molecular docking method on FDA approved drugs, which included Cefpiramide, Cefotiam and Ponatinib, attempted to develop a selective treatment by inhibiting Protein Kinase 1 from T. gondii. The authors found that all compounds could bind strongly to the active site of the protein.…”

“…Currently, available treatments for toxoplasmosis, such as the combination of pyrimethamine with sulfadiazine, have some limitations and side effects that include nausea, headache, folic acid deficiency, aplastic anemia, skin rash and hematologic toxicity ( 8 – 10 ). Investigations into the utility of medicinal plants as potential treatments for toxoplasmosis are currently underway.…”