Antibody array data show activation of kinases in human red blood cells infected with the malaria parasite. Credit: RMIT University
New research on malaria suggests that enzymes of the human host, instead of from the pathogen itself, may provide an effective treatment for a range of infectious diseases, including COVID-19.
The study, conducted by an international team led by Professor Christian Doerig, of RMIT University, outlines a strategy that could save years of drug discovery research and millions of dollars in drug development by redesigning existing treatments designed for others. diseases like cancer.
The approach shows so much promise that it has received government funding for its potential application in the fight against COVID-19.
The study, published in Nature communication, showed that the parasites that cause malaria are highly dependent on enzymes in red blood cells where the parasites hide and proliferate.
It also revealed that drugs developed for cancer, and that inactivating these human enzymes, known as protein kinases, are very effective in killing the parasite and represent an alternative to drugs that target the parasite itself.
This is Professor Christian Doerig, RMIT University. Credit: RMIT University
Lead author, Dr. Jack Adderley, RMIT, said the analysis revealed which of the host cell’s enzymes were activated during infection, revealing new points of confidence of the parasite on its human host.
“This approach has the potential to significantly reduce costs and accelerate the deployment of new and urgent antimalarials,” he said.
“These host enzymes are in many cases the same as those activated in cancer cells, so we can now jump on the back of the existing discovery of cancer drugs and look for a redesign of a drug that is already available or close to the process of medicine development is complete. ”
As well as enabling reintroduction of drugs, the approach can probably reduce the onset of drug resistance, as the pathogen cannot escape by simply mutating the target of the drug, as is the case for most currently obtaining antimalarials.
Doerig, Associate Dean for the Biomedical Sciences Cluster at RMIT and senior author of the paper, said the findings were exciting because drug resistance is one of the biggest challenges in modern healthcare, not just in the case of malaria , but with most infected agents, including a large number of highly pathogenic bacterial species.
New research on malaria suggests that human host enzymes, rather than from the pathogen itself, may provide an effective treatment for a range of infectious diseases, including COVID-19. Credit: RMIT University
“We risk going back to the pre-antibiotic era if we do not solve this resistance problem, which is a clear and current threat to global public health. We need innovative ways to tackle this problem, ”he said.
“By targeting the host and not the pathogen itself, we remove the ability for the pathogen to become rapidly resistant by mutating the target of the drug, because the target is created by the human host, not the pathogen. . “
The Doerig team will now work with the Peter Doherty Institute for Infection and Immunity (Doherty Institute) to investigate potential COVID-19 treatments using this approach, supported by funding from the Victorian Medical Research Acceleration Fund in collaboration with the Bio Capital Impact Fund (BCIF).
Co-researcher on the grant, Dr. Julian Druce of Royal Melbourne Hospital, of the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute, was part of the team that was the first to grow and share the virus that causes COVID-19, and said that the investigation was an important contribution to efforts to defeat the pandemic.
Professor Peter Revill of Royal Melbourne Hospital, Senior Medical Scientist at the Doherty Institute and a leader on Hepatitis B research, said the approach developed by the RMIT team was really exciting.
“This has been successfully proven for other human pathogens, including malaria and Hepatitis C virus, and there are now very real prospects to use it to discover new drug targets for Hepatitis B and COVID-19,” he said.
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Reference: “Analysis of erythrocyte signaling pathways in Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention” 11 August 2020, Nature communication.
DOI: 10.1038 / s41467-020-17829-7
The paper is the result of an international collaboration with RMIT leadership with researchers from Monash University in Melbourne, Dr. Danny Wilson (Malaria Biology Laboratory Head and University of Adelaide and Burnet Institute), Dr Jean-Philippe Semblat (from French government agency Inserm, Paris) and prof. Oliver Billker (Umeå University, Sweden and Sanger Center, UK).
