Computational Antimalarial Drug Discovery

We are applying computational drug discovery  methodologies to identify viable drug targets in Plasmodium falciparum and to design novel drug candidates towards identified targets.

We conducted high throughput docking on novel drug targets identified from the genome of Plasmodium falciparum through querying relevant databases and biochemical pathway analysis.  Chemoinformatics characterization of  identified hit compounds was conducted and validation of antimalarial activities of selected compounds was done by in-vitro antiplasmodial assay (by our collaborators).

We carried out chemogenomics profiling of active compounds, from the in-vitro assay, to predict possible mechanism of action. We are currently conducting “hit” to “lead” optimization of promising compounds.

We also built various qualitative structural activity relationship (QSAR) models from public malarial screen data (including phytochemicals with antimalarial activities) in order to harness valuable information from this data and to identify possible antimalarial drug candidates.

Pictured below is a heatmap of molecular diversity of phytochemicals with anti-malarial activities.

Students:
Egieyeh Samuel Ayodele

Collaborators:

1. Kamal Azzaoui
Centre for Proteomic Chemistry/Insilico Lead Development
Novartis Institute for Biomedical Research
Novartis Campus
Basel, Switzerland
 
2. Claus Ehrhardt
Computer Aided Drug Design
Novartis Institute for Biomedical Research
Novartis Campus
Basel, Switzerland

3. Peter Gedeck
Novartis Institute for Tropical Diseases
Singapore

4. Prof. Sarel Malan
Pharmaceutical Chemistry
School of Pharmacy
University of the Western Cape
Cape Town
South Africa