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

Kadkhodamohammadi, M.; Jaberi, M.; Babaei Akerdi, R.; Karimi, P.; Ahmadi, A.; Aliyar, M.

2019-07-19 bioinformatics
10.1101/560284 bioRxiv
Show abstract

IntroductionThe 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 MethodsIn 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 doesnt 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. ResultsBy 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. ConclusionMoreover, 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.

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