Antibody array data showing activation of kinases in human red blood cells infected with the malaria parasite.
New research into malaria suggests targeting enzymes from the human host, rather than from the pathogen itself, could offer effective treatment for a range of infectious diseases, including COVID-19.
The study, conducted by an international team and led by RMIT University’s Professor Christian Doerig, outlines a strategy that could save years of drug discovery research and millions of dollars in drug development by repurposing existing treatments designed for other diseases such as cancer.
The approach shows so much promise it has received government funding for its potential application in the fight against COVID-19.
The study, published in Nature Communications, demonstrated that the parasites that cause malaria are heavily dependent on enzymes in red blood cells where the parasites hide and proliferate.
It also revealed 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.
Lead author, RMIT’s Dr Jack Adderley, said 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 said
“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 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.
Doerig, Associate Dean for the Biomedical Sciences Cluster at RMIT and senior author of the paper, said the findings were exciting, as drug resistance is one of the biggest challenges in modern healthcare, not only in the case of malaria, but with most infectious agents, including a large number of highly pathogenic bacterial species.
“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. We need innovative ways to address this issue,” he said.
“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 and not by the pathogen.”
Doerig’s team will now collaborate 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 partnership with the Bio Capital Impact Fund (BCIF).
Co-investigator on the grant, Royal Melbourne Hospital’s Dr Julian Druce, of the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute, was part of the team that were first to grow and share the virus that causes COVID-19, and said the research was an important contribution to efforts to defeat the pandemic.
Royal Melbourne Hospital’s Professor Peter Revill, Senior Medical Scientist at the Doherty Institute and a leader on Hepatitis B research, said the approach developed by the RMIT team was truly exciting.
“This has proven successful for other human pathogens including malaria and Hepatitis C virus, and there are now very real prospects to use it to discover novel drug targets for Hepatitis B and COVID-19,” he said.
The paper is the outcome of an RMIT-led international collaboration with researchers from Monash University in Melbourne, Dr Danny Wilson (University of Adelaide’s Malaria Biology Laboratory Head, The Hospital Research Foundation Fellow and Burnet Institute), Dr Jean-Philippe Semblat (from French Government agency Inserm, Paris) and Prof Oliver Billker (Umeå University, Sweden and Wellcome Sanger Institute, UK).
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
Malaria discovery
- Study uncovers the crucial roles of kinesins during the malaria parasite life cycle
Scientists at the University of Nottingham have made a major breakthrough in understanding how malaria parasites divide and transmit the disease, which could be a major step forwards in helping to ...
- How molecular motor proteins are involved in malaria transmission
Scientists have made a major breakthrough in understanding how malaria parasites divide and transmit the disease, which could be a major step forwards in helping to prevent one of the biggest killer ...
- Fact check: False claim that most scientists blamed malaria on dirt in 1900
Multiple researchers were involved in ultimately proving that malaria was transmitted by mosquitos. This was prior to 1900 ...
- NIMR discovers new malaria vector, ‘Anopheles stephensi’ in Northern Nigeria
Prof. Babatunde Salako has said it had discovered a new malaria vector called 'Anopheles Stephensi' in northern Nigeria.
- NIMR discovers new malaria vector in North
Babatunde Salako, on Monday, said it had discovered a new malaria vector called Anopheles stephensi in northern Nigeria. Salako, who spoke with newsmen in Lagos during a birthday ceremony ...
Go deeper with Google Headlines on:
Malaria discovery
Go deeper with Bing News on:
Targeting host enzymes to fight disease
- Monkeypox: New agents to combat a dangerous pathogen
Poxviruses pose a threat to humanity that should be taken seriously, as the current outbreak of monkeypox shows. A research team from the University of Würzburg is now working on the development of ...
- TMPRSS2 protein, a novel target for SARS-CoV-2 drugs
A new study reports the activity of a compound which inhibited TMPRSS2, ultimately preventing severe COVID-19.
- Child, 2, with 'bubble boy' disease cannot get cure because it is not profitable
They are also injected with enzymes to boost immunity ... usually via syrups, to prevent and fight any infections. Regular immunoglobulin therapy is also required to provide the youngster ...
- The continued search for a cure to HIV
At a basic level, the virus’s protein ‘coat’ and the enzymes it uses to gain control of the host cell’s DNA mutate frequently, making it difficult to target with therapeutics. Once a ...
- Coronavirus spike protein activated natural immune response, damaged heart muscle cells
Spike proteins latch onto receptors known as angiotensin-converting enzyme 2 (ACE2 ... s important to get vaccinated and prevent this disease.” “Host natural immunity is the first line ...
