همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

New inhibitors of the Toxoplasmosis by in-silico drug repurposing

نویسندگان :

Milad Jaberi¹ Masoud Aliyar² Mosleh Kadkhodamohammadi³ Parva Karimimousivandi⁴

1- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2- Faculty of Science, Golestan university, Shahid Beheshti Street, Gorgan, Golestan province, Iran 3- 2. Faculty of Medicine, Central Building, Tabriz University of Medical Sciences, University Street, Tabriz, Iran 4- 3. Friedrich Schiller University Jena, faculty of sciences, Fürstengraben 1, 07743 Jena, Germany

کلمات کلیدی :

Toxoplasma Gondii،Drug repurposing،Docking،Molecular Dynamics

چکیده :

Introduction: The common treatment for toxoplasmosis was pyrimethamine. It has been noticed in recent years that this parasite becomes resistant to this treatment and it thus needs immediate alternative therapies. Materials and Methods: In this study, using drug re-purposing and in silico methods we tried to make selective treatment by inhibiting the Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii which does not exist in mammalians. We screened the FDA approved drugs by molecular docking and, after ranking them by their binding energies and inspecting the top scoring ones, we selected Cefpiramide, Ceftriaxone and Cefotiam as the hit compounds. Afterwards, we used molecular dynamic simulations to evaluate the hit compounds in a much more realistic environment. Results: Through analyzing the results, we have found that all of the hit compounds are effective and can be strongly bound to the active site of the protein. They may therefore be potential candidates for the inhibition of Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii. Conclusion: Given that the predicted compounds are FDA approved drugs, their toxicity profiles are established and their potentially predicted use can be evaluated in clinical trials.