Led by Makedonka Mitreva, PhD, the research found that repurposed GPCR antagonists and new analogs can reduce adult worm burden and fertility.
Researchers at WashU Medicine have reported a promising new strategy for fighting filarial worms, a group of parasites that cause serious chronic diseases such as river blindness. The study, led by Makedonka Mitreva, PhD, Gordon R. Miller Professor of Medicine, Departments of Medicine and Genetics, tested repurposed human GPCR antagonists alongside a series of newly designed analogs — an effort led by James Janetka, PhD, Carl Frieden Distinguished Professor, Department of Biochemistry and Molecular Biophysics — to see whether they could kill adult worms or reduce their ability to reproduce. The study was supported by the NIAID and published August 13, 2026 in Journal of Medicinal Chemistry.
The team found that several compounds showed strong activity against adult parasites in laboratory tests, and a few also worked in animal studies. The histamine antagonist, Clemizole, and its analog C-8 were especially effective, significantly reducing worm burdens, while S-17 and PMZ-6 lowered the worms’ reproductive output. The researchers also identified likely parasite targets, including gar-3 and ser-7, suggesting that interfering with worm GPCR signaling may be a viable way to develop much-needed macrofilaricidal drugs.
By combining drug re-purposing with medicinal chemistry and genetic screening, the study highlights a promising path toward treatments that could help eliminate adult filarial worms more effectively.
Rosa BA, Han Z, Arun A, Tricoche N, Peguero R, Banas V, Shadrick M, Fath M, Suksomboon P, Bharti S, Bancks M, Rehborg EG, Zamanian M, Cho-Ngwa F, Lustigman S, Janetka JW, Mitreva M. Discovery of GPCR Antagonists with Potent In Vitro and In Vivo Macrofilaricidal Activity. J Med Chem. 2026 Aug 13;69(15):19130-19161. doi: 10.1021/acs.jmedchem.6c01435. PMID: 42470372.