Holistic Drug Discovery and Development (H3D) Centre, University of Cape Town

The Holistic Drug Discovery and Development (H3D) Centre is an interdisciplinary research unit at the University of Cape Town. The Centre’s mission is to discover and develop innovative, lifesaving medicines for diseases that predominantly affect African patients. There is a key focus on building drug discovery capacity in Africa and training the next generation in drug discovery-related sciences. H3D has research programs in the areas of malaria, tuberculosis, antimicrobial resistance, and more recently COVID-19.

Laboratory Contributions

H3D has extensive experience in malaria drug discovery with a track record in progressing projects from hit identification to candidate selection stages. Capabilities include the following:

• Medicinal chemistry
• Computer-aided drug design (CADD)
• ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity)
• Pharmacokinetics and metabolite identification
• Malaria biology
  • Asexual blood stage screening
  • In vivo efficacy studies in a NSG mouse model of malaria infection
  • Whole cell washout assays for targeted covalent inhibitors
  • Drug accumulation assays via the inoculum effect
  • Drug-drug interaction assays (isobologram analysis)
  • Resistance selection and cross resistance studies
  • β-haematin inhibition and cellular haem fractionation assays
  • Fluorescently-labelled probes for microscopy (live imaging)
  • Affinity-based target identification (matrix-based and matrix-free approaches)
• Enzymology/biochemical assay development (Plasmodium kinase platform)