# Protein arginine methyltransferases in protozoan parasites: a new path for antiparasitic chemotherapy?

**Authors:** Gustavo D. Campagnaro, Sébastien Pomel

PMC · DOI: 10.15698/mic2026.02.869 · 2026-02-12

## TL;DR

This paper explores how protein arginine methyltransferases (PRMTs) in protozoan parasites could be targeted for new antiparasitic treatments.

## Contribution

The paper proposes repurposing existing PRMT inhibitors for antiparasitic chemotherapy by exploiting differences between parasite and mammalian PRMTs.

## Key findings

- PRMTs are essential for the survival and infection processes of pathogenic protozoan parasites.
- Differences between parasite and mammalian PRMTs suggest potential for selective drug targeting.
- Existing PRMT inhibitors could be redeveloped as antiparasitic agents.

## Abstract

Protein arginine methyltransferases (PRMTs) catalyse the transference of methyl groups from S-adenosylmethionine to arginine residues in substrate proteins, a post-translational modification widespread among eukaryotes. The change in size and hydrophobicity of the methylated arginine residue impacts on how a protein interacts with other macromolecules and affects several cellular processes, including intracellular signaling, DNA replication and repair, and control of gene expression. As a result, PRMTs became attractive targets for chemotherapy, and several PRMT inhibitors are going through clinical trials for cancer treatment. In protozoan parasites, PRMTs play fundamental roles during development, stage differentiation and infection processes. We here review the activity and the relevance of PRMTs for the survival of pathogenic kinetoplastids, apicomplexans and amoebas, highlight differences observed between PRMTs expressed in these organisms and their mammalian orthologues, and suggest that these enzymes can be exploited to combat parasitic infections. We propose that the arsenal of inhibitors developed to target mammalian PRMTs could be reassigned to allow the identification of new scaffolds to be explored as antiparasitic agents, either as sole chemotherapy or by improving the effectiveness of current antiparasitic drugs.

## Linked entities

- **Chemicals:** S-adenosylmethionine (PubChem CID 34755)

## Full-text entities

- **Genes:** ARHGEF5 (Rho guanine nucleotide exchange factor 5) [NCBI Gene 7984] {aka GEF5, P60, TIM, TIM1}, WDR77 (WD repeat domain 77) [NCBI Gene 79084] {aka HKMT1069, MEP-50, MEP50, Nbla10071, p44, p44/Mep50}, PRMT7 (protein arginine methyltransferase 7) [NCBI Gene 54496] {aka SBIDDS}, PRMT1 (protein arginine methyltransferase 1) [NCBI Gene 3276] {aka ANM1, HCP1, HRMT1L2, IR1B4}, PRMT3 (protein arginine methyltransferase 3) [NCBI Gene 10196] {aka HRMT1L3}, CARM1 (coactivator associated arginine methyltransferase 1) [NCBI Gene 10498] {aka PRMT4}, PRMT6 (protein arginine methyltransferase 6) [NCBI Gene 55170] {aka HRMT1L6}, KRT18 (keratin 18) [NCBI Gene 3875] {aka CK-18, CYK18, K18}, TSN (translin) [NCBI Gene 7247] {aka BCLF-1, C3PO, RCHF1, REHF-1, TBRBP, TRSLN}, PRMT5 (protein arginine methyltransferase 5) [NCBI Gene 10419] {aka HRMT1L5, HSL7, IBP72, JBP1, SKB1, SKB1Hs}, PRMT2 (protein arginine methyltransferase 2) [NCBI Gene 3275] {aka HRMT1L1}
- **Diseases:** birth defects (MESH:D000014), cryptosporidiosis (MESH:D003457), deaths (MESH:D003643), amoebic keratitis (MESH:D007634), Acanthamoeba ocular infections (MESH:D000562), MAMMALIAN (MESH:C000655084), encephalitis (MESH:D004660), T. brucei infections (MESH:D007239), intestinal amebiasis (MESH:D004404), toxicity (MESH:D064420), miscarriages (MESH:D000022), OTHER PROTOZOA (MESH:D058497), parasitic infections (MESH:D010272), congenital toxoplasmosis (MESH:D014125), African Animal Trypanosomiasis (MESH:D014353), Chagas' disease (MESH:D014355), hydrocephalus (MESH:D006849), Plasmodium infection (MESH:D008288), Infectious Diseases (MESH:D003141), toxoplasmosis (MESH:D014123), cyst (MESH:D003560), cutaneous leishmaniasis (MESH:D016773), meningoencephalitis (MESH:D008590), cancer (MESH:D009369), leishmaniases (MESH:D007896), retinochoroiditis (MESH:D000080365), NTDs (MESH:D058069)
- **Chemicals:** EPZ015666 (MESH:C000599896), 3,5-bis-(3-bromo-4-hydroxybenzylidene)thiopyran-4-one (-), Diminazene (MESH:D004133), homocysteine (MESH:D006710), arginine (MESH:D001120), benznidazole (MESH:C009999), ellagic acid (MESH:D004610), Suramin (MESH:D013498), ADMA (MESH:C018524), sinefungin (MESH:C006235), glucose (MESH:D005947), Eflornithine (MESH:D000518), Melarsoprol (MESH:D008549), proline (MESH:D011392), adenosine (MESH:D000241), propamidine (MESH:C005555), BVT-948 (MESH:C487115), Fexinidazole (MESH:C038307), nitrogen (MESH:D009584), SDMA (MESH:C024917), 1-benzyl-3,5-bis-(3-bromo-4-hydroxybenzylidene)piperidin-4-one (MESH:C000624200), metronidazole (MESH:D008795), tricarboxylic acid (MESH:D014233), diminazene aceturate (MESH:C003915), Isometamidium (MESH:C000702), Pentamidine (MESH:D010419), polyhexamethylene biguanide (MESH:C031233), -monomethylarginine (MESH:D019323), Onametostat (MESH:C000631033), S-adenosyl-methionine (MESH:D012436), chlorhexidine (MESH:D002710), Nifurtimox (MESH:D009547), artemisinin (MESH:C031327)
- **Species:** Legionella sp. D (species) [taxon 66972], Cryptosporidium parvum (species) [taxon 5807], Trypanosoma vivax (species) [taxon 5699], Acanthamoeba sp. (species) [taxon 5756], Trypanosoma evansi (species) [taxon 5697], Leishmania braziliensis (species) [taxon 5660], Trypanosoma brucei (species) [taxon 5691], Pf [taxon 1985359], Entamoeba invadens (species) [taxon 33085], Homo sapiens (human, species) [taxon 9606], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Leishmania major (species) [taxon 5664], Trypanosomatidae (family) [taxon 5654], Leishmania donovani (species) [taxon 5661], Glossina (tsetse flies, genus) [taxon 7393], Dictyostelium discoideum (species) [taxon 44689], Entamoeba histolytica (species) [taxon 5759], Phytomonas (genus) [taxon 5706], Naegleria fowleri (brain-eating amoeba, species) [taxon 5763], Cyclospora sp. (species) [taxon 44418], Leishmania infantum (species) [taxon 5671], Babesia sp. (species) [taxon 35084], Mus musculus (house mouse, species) [taxon 10090], Trypanosoma congolense (species) [taxon 5692], Crithidia (genus) [taxon 5655], Balamuthia mandrillaris (species) [taxon 66527], Lotmaria (genus) [taxon 1620386], Trypanosoma cruzi (species) [taxon 5693], Toxoplasma gondii (species) [taxon 5811], Acanthamoeba castellanii (species) [taxon 5755]
- **Mutations:** arginine-glycine

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12925635/full.md

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Source: https://tomesphere.com/paper/PMC12925635