Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372430 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0384 (Electronic) Linking ISSN: 00039861 NLM ISO Abbreviation: Arch Biochem Biophys Subsets: MEDLINE
    • Publication Information:
      Publication: <2000- > : San Diego, CA : Elsevier
      Original Publication: New York, NY : Academic Press
    • Subject Terms:
      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*; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/chemistry ; Molecular Docking Simulation ; Protozoan Proteins/antagonists & inhibitors ; Protozoan Proteins/chemistry ; Protozoan Proteins/metabolism
    • 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.)
    • Contributed Indexing:
      Keywords: Cryptosporidium parvum; Drug discovery; IMPPAT database; Lactate dehydrogenase; MD simulation; S. aromaticum
    • Accession Number:
      0 (Phytochemicals)
      EC 1.1.1.27 (L-Lactate Dehydrogenase)
      0 (Antiprotozoal Agents)
      0 (Protozoan Proteins)
    • Publication Date:
      Date Created: 20240818 Date Completed: 20240910 Latest Revision: 20241101
    • Publication Date:
      20241101
    • Accession Number:
      10.1016/j.abb.2024.110124
    • Accession Number:
      39154815