Dr Fortunate Mokoena has a vision. This senior lecturer in biochemistry at the Faculty of Natural and Agricultural Sciences at the North-West University (NWU) wants to make the continent she calls home a better, safer place for its citizens.
She hopes to do this by helping to eliminate malaria.
“Many of us born on the African continent grew up wanting to make a lasting contribution to Africa's economic emancipation, growth and development. I have focused on studying diseases that plague Africa the most, hoping to contribute to drug discovery to eradicate tropical diseases that disproportionately affect the continent. I believe that the reduction and eventual eradication of malaria on the continent, which requires drug discovery, is essential to the continent's success,” she explains.
In 2021, there were 609 000 deaths from malaria, predominantly in sub-Saharan Africa, where tropical climates facilitate the spread of mosquito vectors, severely impacting pregnant women and young children.
Drug resistance poses a significant challenge in combatting malaria. On the other hand, the recent development of an effective vaccine offers hope for reducing transmission, particularly in vulnerable regions.
These anomalies underscore the need for ongoing research into novel treatments, while also integrating vaccines, insecticides and drugs so that they work together to beat the disease.
Dr Mokoena says she and her team, which consists of four MSc students, Tlhalefo Ntseane, Thato Matlhodi, Ofentse Mafethe and Lisema Makatsela, aims to find new drugs for treating malaria by studying a specific protein essential for the malaria parasite's survival, called PfHsp90.
“We use computer simulations and lab experiments to identify and optimise potential drug compounds. These compounds are tested on PfHsp90 in the lab, and their effects are also evaluated on both malaria parasites and human cells. By combining results from different tests, we determine if the compounds have the potential to be effective antimalarial drugs.”
This collaborative project has identified some hit compounds* targeting or inhibiting, PfHsp90, with potent activity against the P.falciparum asexual stage parasite. The hit compounds have also been demonstrated to inhibit and bind the target protein, without impacting the human counterpart of the protein.
“The targeting of PfHsp90 can slow down or reduce the likelihood of drug resistance. The detrimental effect of PfHsp90 on parasite survival was demonstrated using known inhibitors developed as anti-cancer agents. Our study used computer-aided drug discovery technology to identify new compounds that are toxic to the parasite and are capable of inhibiting PfHsp90.”
Most of these compounds had low to no cytotoxicity to human cells, making them promising starting points for drug discovery. “Improved potency and affinity towards PfHsp90 could result in the compound providing a promising lead for antimalarial drug discovery.”
Putting an end to malaria in Africa will save lives, enhance public health, reduce poverty, improve economic stability and relieve the burden on healthcare systems. Thanks to people like Dr Mokoena and her team, the research being done could lead to greater social and developmental progress across the continent.
* A hit compound is a molecule that shows the desired type of activity in a screening assay. In the drug discovery process, a hit is a compound that displays desired biological activity towards a drug target and reproduces this activity when retested.
Dr Fortunate Mokoena.
