1. Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations.
- Author
-
Altwaim SA, Alsaady IM, Gattan HS, Alruhaili MH, Khateb AM, El-Daly MM, Dubey A, Dwivedi VD, and Azhar EI
- Subjects
- Antiprotozoal Agents pharmacology, Antiprotozoal Agents chemistry, Molecular Docking Simulation, Protozoan Proteins antagonists & inhibitors, Protozoan Proteins chemistry, Protozoan Proteins metabolism, Cryptosporidium parvum enzymology, Cryptosporidium parvum drug effects, Syzygium chemistry, Phytochemicals chemistry, Phytochemicals pharmacology, L-Lactate Dehydrogenase antagonists & inhibitors, L-Lactate Dehydrogenase chemistry, L-Lactate Dehydrogenase metabolism, Molecular Dynamics Simulation
- Abstract
Cryptosporidium parvum (C. parvum), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of C. parvum, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of C. parvum. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the Syzygium aromaticum (S. aromaticum). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from S. aromaticum could be further explored as potential hit candidates for developing effective drugs against C. parvum infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors., Competing Interests: Declaration of competing interest The author(s) declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF