New research into malaria suggests targeting enzymes from the human host rather than the pathogen itself could offer effective treatment for a range of infectious diseases.
Writing in the journal Nature Communications, an Australian-led team outlines a strategy it says could save years of drug discovery research and development by repurposing existing treatments designed for other diseases such as cancer.
On the basis of progress to date, funding has been provided in Australia to explore its potential application against COVID-19.
The study, which was led by RMIT University and involved researchers from Australia, France, Sweden and the UK, demonstrates, they say, that the parasites that cause malaria are heavily dependent on enzymes in red blood cells where the parasites proliferate.
It also reveals that drugs developed for cancer, and which inactivate these human enzymes, known as protein kinases, are highly effective in killing the parasite and represent an alternative to drugs that target the parasite itself.
RMIT’s Jack Adderley, the paper’s lead author, says the analysis revealed which of the host cell enzymes were activated during infection, revealing novel points of reliance of the parasite on its human host.
“This approach has the potential to considerably reduce the cost and accelerate the deployment of new and urgently needed antimalarials,” he says.
“These host enzymes are in many instances the same as those activated in cancer cells, so we can now jump on the back of existing cancer drug discovery and look to repurpose a drug that is already available or close to completion of the drug development process.”
As well as enabling the repurposing of drugs, the researchers say, their approach is likely to reduce the emergence of drug resistance, as the pathogen cannot escape by simply mutating the target of the drug, as is the case for most currently available antimalarials.
“We are at risk of returning to the pre-antibiotic era if we don’t solve this resistance problem, which constitutes a clear and present danger for global public health,” says RMIT’s Christian Doerig, the research leader. “We need innovative ways to address this issue
“By targeting the host and not the pathogen itself, we remove the possibility for the pathogen to rapidly become resistant by mutating the target of the drug, as the target is made by the human host, not the pathogen.”
Doerig’s team will now work with researchers at Australia’s Doherty Institute for Infection and Immunity to investigate potential COVID-19 treatments using their approach.
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