In silico targeting cysteine protease 2 of Giardia lamblia by Origanum vulgare L. flavonoids as potential inhibitors

Subject Areas : Computational and Theoretical Studies Related to Different Aspects of Phytochemistry

Amir Abbas Barzegari ¹ , Milad Zare ² , Sepideh Parvizpour ³

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Received: 2024-07-26 Accepted : 2024-12-28 Published : 2024-12-30

Keywords: Cysteine proteases, Flavonoids, Giardia lamblia, Marjoram, Molecular dockings,

Abstract :

Giardiasis, caused by Giardia lamblia, is a prevalent and problematic infection. Current treatments, such as metronidazole have some limitations. Flavonoids may possess anti-giardia properties. As CP2 (giardipain-1) plays a critical role in the parasite's pathogenicity, the present study aimed to discover if the flavonoids of marjoram can target CP2 and inhibit it. After modeling the CP2 spatial structure and obtaining the chemical structure of flavonoids, molecular docking was performed using PyRx. Subsequently, pharmacokinetics and the toxicity of flavonoids with the highest binding affinity for CP2 were investigated. Finally, molecular dynamics simulation was conducted on CP2 and the final candidate. Among marjoram flavonoids, isovitexin, cosmosiin, and apigenin 7-O-methylglucuronide exhibited the highest binding affinity for CP2. However, toxicity studies revealed that isovitexin and cosmosiin are mutagens. Therefore, only apigenin 7-O-methylglucuronide can be considered a potential drug for treating giardiasis. Nevertheless, further studies are needed to confirm this hypothesis.

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