Dr Olatomide Fadare Nigerian-led research team at Obafemi Awolowo University, Ile-Ife, Osun State, has recorded a major scientific breakthrough in the global fight against malaria.
The team successfully determined and deposited the first-ever crystal structure of Plasmodium falciparum transketolase bound to an inhibitor in the Protein Data Bank.
The milestone, achieved at the laboratory of Dr Olatomide Fadare, Associate Professor of Chemistry at OAU, marks the first Protein Data Bank structure authored entirely by Nigerian scientists.
Fadare, originally trained as a synthetic organic chemist, has evolved into a leading medicinal chemist, combining organic synthesis, bioinformatics and biological testing to design novel drug candidates targeting malaria — a disease that remains endemic in sub-Saharan Africa.
Driven by growing resistance to artemisinin-based combination therapies, he said his research is focused on developing the next frontline antimalarial drug.
Speaking in an interview with PUNCH Online, Dr Olatomide Fadare said:
“You know, Fansidar used to be a three-tablet therapy taken at once. Over time, resistance developed. That is the story of malaria treatment.
If we don’t continue to design new therapies that target different pathways, the parasite will always catch up with us.”
The breakthrough emerged from a collaboration of internationally based Nigerian scientists, including Dr Olawale Raimi of the University of Dundee, Scotland; Dr Abiodun Ogunjimi of Mount Sinai Hospital, Toronto; Prof Olubanke Ogunlana of Covenant University, Ota, Ogun State, and Dr Oluseyi A. Vanderpuye of Fayetteville State University, United States, among others.
Central to the team’s research is transketolase, a critical enzyme in Plasmodium falciparum, the parasite responsible for the deadliest form of malaria.
For years, rational drug design targeting this enzyme was hindered by the absence of experimentally determined crystal structures in the Protein Data Bank, with researchers globally relying largely on computational models.
That barrier, Fadare said, has now been broken.
“We carried out protein engineering, produced the protein and successfully crystallised it. Getting to the point where you can create a crystal from your protein is highly advanced science.
There is a global repository called the Protein Data Bank where scientists deposit protein crystal structures. Most of the structures there were deposited by researchers from Western countries. You rarely find deposits from Africa. But now, instead of being users, we have become depositors,” he said.
He described the development as “very, very significant.”
“It demonstrates that Nigerians can compete on the global stage. What makes it even more remarkable is that everyone listed on that deposit is Nigerian,” he added.
While Fadare’s laboratory in Ile-Ife designed and synthesised new chemical entities, collaborators abroad handled cloning, protein expression, crystallisation, inhibition studies, protocol optimisation and data analysis.
“We are running interconnected projects across Nigeria, the UK, Canada and the US. This positions Nigeria as a serious contributor to next-generation antimalarial drug discovery,” he said.
Beyond the structural breakthrough, the team has already identified four to five small molecules that strongly inhibit the parasite’s transketolase enzyme without significantly affecting the human equivalent.
“We believe that if we inhibit this protein, the metabolic processes it controls in the parasite will slow down or stop completely. That means the parasite cannot grow or replicate, and eventually it dies,” Fadare explained.
However, he noted the importance of selectivity.
“Humans also express transketolase. The difference between the human and parasite enzymes is small but significant — significant enough to exploit. It is possible to design a selective inhibitor that targets the parasite without harming the human host,” he said.
The next phase involves refining and optimising these lead compounds to improve potency and specificity.
“We already have very good leads that we want to pursue,” he said.
Fadare used the opportunity to highlight broader challenges facing scientific research in Africa, particularly dependence on imported medicines and technologies.
“One of our biggest problems is that we depend almost entirely on Western therapies. During COVID-19, none of the vaccines came from Africa. Even mass production infrastructure was absent,” he said.
According to him, sustained investment in science and technology is critical if Nigeria hopes to achieve health-sector independence.
“What happens in science translates directly into solutions in the health sector. Long-term, constructive investment in research is what produces breakthroughs,” he added.
He also raised concerns about brain drain, noting that many of the bright students he mentors eventually leave the country due to limited industrial opportunities.
“Virtually every active pharmaceutical ingredient used in Nigeria is imported, mostly from India or China. We have the scientific expertise to produce them locally, but the industry has not matured to that level,” he said.
“That is why we keep losing brilliant minds. I consider it a tragedy for the nation,” he added.
Despite the challenges, Dr Olatomide Fadare said mentorship remains central to his work.
“If you want to push the frontiers of science, you cannot do it alone. You need young, smart, highly motivated people,” he said.
By grooming young scientists and fostering international collaborations, he hopes his laboratory will serve as a model for what is possible within Nigeria.
“With the right support, what we are doing can cause a tectonic shift in the pharmaceutical industry.
We have not received funding from the government or organisations yet, but we continue to push forward. If we get the right support, the impact will be massive,” he said.
