Another win for H3D as Kelly Chibale achieves A-rating
9 Jan 2018 - 08:00
Professor Kelly Chibale
[Article adapted from UCT Science Faculty news]
Having grown up in the villages and townships of Zambia, Professor Kelly Chibale (Member of the IDM and of the Department of Chemistry, Faculty of Science, UCT) became well acquainted with the ravages of malaria at a young age. Now, inspired by a deep spirituality and a love of chemistry, his invaluable contribution to the ongoing battle against this disease – amongst others – has been awarded an 'A' rating by the National Research Foundation. A-rated researchers are unequivocally recognised by their peers as leading international scholars in their respective fields, for the high quality and impact of their research outputs over the past eight years, taking into consideration the evaluation made by local and international peers.
“To know that peers in my field think so highly of me is humbling,” says Chibale, adding that “although this means a lot to me personally, the work on which my rating is based is not mine alone. It is a result of a collective effort … I share this A rating with all my collaborators. I could not have done it without God and them.”
With an academic background in chemistry, the main thrust of Chibale’s research in recent years can be described as drug discovery for communicable parasitic and bacterial diseases – the former including malaria and schistosomiasis (or bilharzia), the latter tuberculosis and other drug-resistant infections of bacterial origin. “Our use-inspired drug discovery basic science research has led to historical scientific breakthroughs and, in the process, advanced both basic and clinical sciences at several levels,” he says.
Establishment of H3D
It is Chibale’s establishment of UCT’s Drug Discovery and Development Centre (H3D; http://www.h3d.uct.ac.za/) – of which he is director – that has made much of this research possible. Set up to bridge the gap between laboratory and patient, H3D integrates medicinal chemistry, biology, pharmacology as well as drug metabolism and pharmacokinetics studies. It is the first and only centre of its kind on the African continent and also one of the rare integrated drug discovery centres set up within an academic environment worldwide.
Using both genomic and proteomic approaches to clarify how new drugs work through the identification of their biological target, Chibale and his lab have contributed to fundamental understanding and basic scientific knowledge. Within the context of malaria, these approaches led to the identification of the human malaria parasite enzyme known as PfPI4K as the target for MMV048, an antimalarial clinical drug candidate that was found to be effective against resistant strains and with activity across the entire parasite life cycle. It was also shown to have the potential to cure and protect in a single dose due to its inhibition of PfPI4K, which is involved in the correct membrane assembly around daughter parasites as they leave infected human red blood cells (RBCs) to infect other healthy RBCs. Inhibition of PfPI4K results in defects in the new plasma membrane.
Chibale and his team’s work around MMV048 has been significant for a number of reasons. It was the first time a chemical proteomics approach was used to identify a malaria drug target; MMV048 was the first and only molecule that reduces the activity of the PfPI4K enzyme to have progressed to Phase I human clinical studies and it is the first known malaria kinase inhibitor to enter the clinic. Lastly, the advancement of MMV048 marks the first time an Africa-led international drug development effort has taken a small molecule from screening through to human clinical trials, all through modern drug discovery techniques.
In 2016, H3D and its partners identified a second preclinical development candidate – UCT943 – which may be even more potent against the malaria parasite and easier to formulate.