An international team of researchers have developed a new drug called covalent kinase inhibitor which they say, has potential to combat the spread of treatment-resistant malaria.
This is according to a report entitled, ‘Targeting Pf CLK3 with Covalent inhibitors: A Novel Strategy for Malaria Treatment.’
Experts say covalent inhibitors form bond with their proteins, usually irreversibly modifying them.
The team, consisting of chemists and bioscientists from the University of Glasgow led the development of the new drug.
In a paper published in the Journal of Medicinal Chemistry in November they outlined how the treatment could be more effective than current medications at all stages of malaria infection.
The researchers said covalent Kinase inhibitor could also work as a single -dose treatment.
The report stated that the breakthrough was the first to adapt an approach from cancer treatments to tackle malaria.
The researchers explained that the new drug works by permanently disabling a protein that Plasmodium falciparum, one of the mosquito-borne parasites which spreads malaria, uses to duplicate itself inside the human body.
“Nearly a quarter of a billion cases of malaria are reported around the world every year, killing more than 600,000 people annually.
“The new drug could help to overcome the growing problem of Plasmodium falciparum’s resistance to artemisinin, the current Frontline treatment for malaria infections.’”
Andrew Jamieson, Professor of Chemical Biology at the University of Glasgow’s School of Chemistry, one of the paper’s corresponding authors said that during the pandemic, global progress against malaria stalled.
He said this was due to difficulty of access to treatment, while parasites simultaneously developed increasing resistance to current drugs.
Jamieson said: “We wanted to see whether a type of drug called a covalent kinase inhibitor, which has been used successfully in some cancer treatments, could provide an entirely new way to tackle malaria parasites.
“A fresh approach to medication could help us shore up our defences against malaria in the years to come.”
The researchers said the new drug works by targeting a protein called Pf CLK3, which plays a vital role in the parasite’s ability to splice Ribonucleic acid(RNA).
By firmly attaching itself to the protein, the drug molecule essentially turns off the parasite’s method of replicating itself to the bloodstream, killing it before it can spread.
Skye Brettell, whose doctoral research as a PhD student in the School of Chemistry was part of the development of the drug, said that covalent kinase inhibitors were commonly used in oncology.
According to her, the frequent drawback is that while targeting cancer proteins, these drugs often affect other proteins as well, leading to side effects.
However, Brettell assured that the molecule they developed was much more focused on its target.
“It has a special chemical ‘grappling hook’ that ensures it sticks only to the PfCLK3 protein, which could help it treat malaria without causing unwanted effects in humans,” she said.
The researchers ran the drug through an extensive battery of tests while their colleagues at the University of Edinburgh helped them test the drug on isolated proteins.
Using mass spectrometry, an instrument used to separate and measure components of a physical phenomenon, they showed that the drug was permanently binding to its targets.
Skye added that these were really robust results, which showed that the drug could withstand the challenges it might face inside the parasite.
She expressed optimism that the parasite was unlikely to develop resistance to it.
NAN
