Unit | Parasite Chemotherapy

The Parasite Chemotherapy Unit (PCU) is a drug discovery centre for protozoan parasites. We have over 20 years of experience in assay development and drug efficacy testing for the causative agents of malaria (Plasmodium spp.), African sleeping sickness (Trypanosoma brucei), Chagas disease (T. cruzi), leishmaniasis (Leishmania spp.) and diarrhoea (Entamoeba and Giardia). Primary and secondary in vitro assays are combined with mouse models of disease (for African trypanosomes and malaria) and molecular approaches to drug action and resistance. The PCU works closely with product development partnerships such as the Medicines for Malaria Venture (MMV), DNDi or GALVmed, with academic partners around the world and with pharmaceutical companies. The PCU has been instrumental in the development of several clinical candidates, including fexinidazole for human African trypanosomiasis (HAT) and artefenomel for malaria. 

Drug Discovery

A substantial part of the research is focused on the development of novel in vitro assays and in vivo models. Drug discovery activities are complemented by preclinical studies on drug absorption and pharmacokinetics. Molecular biology and bioinformatics approaches are also used to investigate mechanisms of drug resistance and mode of drug action. The unit has a screening mandate from the Medicines for Malaria Venture (MMV) Foundation and has become the main WHO/TDR centre for in vitro screening against protozoan parasites.

Eastern African Network for Trypanosomiasis (EANETT)

As well as working on new drugs, the group also collaborates with African partner institutes in the Eastern Africa Network for Trypanosomiasis (EANETT) in the area of sleeping sickness research and control. The Swiss Agency for Development and Cooperation (SDC) has awarded the network a second phase of support for 2004-2006. A key objective for this phase was to involve the network in international activities, with access to additional funding.

Trypanosome Transmission

Another element of the activities is to study the transmission of trypanosomes by the tsetse fly vector in order to gain more knowledge about the life cycle of the parasite and the function of certain surface proteins.

Ajayi O et al. Discovery of an orally active nitrothiophene-based antitrypanosomal agent. Eur J Med Chem. 2024;263:115954. DOI: 10.1016/j.ejmech.2023.115954

Baert L et al. Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. PLoS Negl Trop Dis. 2024;18(1):e001155. DOI: 10.1371/journal.pntd.0011559

Bizzarri L et al. Studying target-engagement of anti-infectives by solvent-induced protein precipitation and quantitative mass spectrometry. ACS Infect Dis. 2024(in press). DOI: 10.1021/acsinfecdis.4c00417

Bravo P et al. Integral solvent-induced protein precipitation for target-engagement studies in Plasmodium Falciparum. ACS Infect Dis. 2024(in press). DOI: 10.1021/acsinfecdis.4c00418

Calic P.P.S et al. Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3. Eur J Med Chem. 2024;276:116677. DOI: 10.1016/j.ejmech.2024.116677