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PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of Entamoeba invadens

Rigoberto Ortiz-Hernández1, Elmer Joel Millán-Casarrubias2, Jeni Bolaños1

  • 1Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico.

Molecules (Basel, Switzerland)
|January 11, 2025
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) is crucial for parasitic protozoan stage conversion. Inhibiting EiPRMT5 in Entamoeba invadens reduces parasite viability and encystment, offering a potential strategy against amebiasis.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein arginine methyltransferase 5 (PRMT5) regulates cellular processes, including stage conversion in parasitic protozoans.
  • Entamoeba histolytica causes human amebiasis, with distinct trophozoite and cyst stages.
  • Studying Entamoeba differentiation is challenging due to limited in vitro encystment protocols, necessitating models like Entamoeba invadens.

Purpose of the Study:

  • To investigate the role of PRMT5 in Entamoeba invadens differentiation.
  • To identify and characterize the PRMT5 enzyme in E. invadens (EiPRMT5).
  • To evaluate the potential of EiPRMT5 as a drug target for amebiasis.

Main Methods:

  • Demonstration of symmetric dimethyl arginine (sDMA) presence and its increase during E. invadens encystment.
  • Identification and 3D structural modeling of EiPRMT5.
  • Molecular docking of the PRMT5 inhibitor EPZ015666 with EiPRMT5.
  • Assessment of EPZ015666's effect on E. invadens trophozoite viability and encystment.

Main Results:

  • Symmetric dimethyl arginine (sDMA) was detected in E. invadens and increased during encystment.
  • The PRMT5 enzyme from E. invadens (EiPRMT5) was identified and modeled.
  • Molecular docking predicted EPZ015666 binds to the EiPRMT5 active site.
  • EPZ015666 treatment decreased E. invadens trophozoite viability and inhibited encystment.

Conclusions:

  • EiPRMT5 plays a role in E. invadens differentiation.
  • The PRMT5 inhibitor EPZ015666 demonstrates anti-parasitic activity against E. invadens.
  • EiPRMT5 represents a promising therapeutic target for controlling amebiasis transmission.
Keywords:
Entamoeba invadensPRMT5encystmentsymmetric arginine dimethylation

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