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
- Drug-discovery collaboration finds potential new antimalarial drug candidateson April 22, 2021 at 7:49 pm
Potential new antimalarial drug candidates are being developed through an extended drug-discovery collaboration between Australian medical research institute WEHI and Janssen Pharmaceutica NV. The ...
- Collaboration with Johnson & Johnson Innovation to jump-start search for new malaria drugson April 22, 2021 at 7:12 am
Potential new antimalarial drug candidates are being developed through an extended drug-discovery collaboration between Australian medical research institute WEHI and Janssen Pharmaceutica NV. The ...
- I’ve survived being deaf in hearing worldon April 21, 2021 at 4:59 pm
But it was not until she was in primary school that she discovered her hearing problem. "It dawned on me when I was in Standard Three that I couldn't hear well and it saddened me as I grew up," she ...
- Rwanda to continue using coartem to treat malaria — RBCon April 19, 2021 at 7:16 am
Although one component of coartem, a drug used to treat malaria is weakening, there are no plans to discontinue its use because its effectiveness is currently undisputable. The Head of the Malaria and ...
- Mysteries of Malaria Infections Deepen After Study Where Volunteers Were Injected With Malaria Parasiteson April 18, 2021 at 8:16 pm
Scientists have discovered that tracking malaria as it develops in humans is a powerful way to detect how the malaria parasite causes a range of infection outcomes in its host. The study, found some r ...
Go deeper with Google Headlines on:
Malaria discovery
Go deeper with Bing News on:
Targeting host enzymes to fight disease
- COVID-19: ‘Ring vaccination’ can teach us how to target limited supplyon April 22, 2021 at 7:55 am
While experts say COVID-19 and its spread pose unique challenges in deploying ring vaccination by the book, the principles behind it can guide vaccine prioritization.
- Can an immunosuppressive cancer drug promote SARS-CoV-2 entry into host cells?on April 20, 2021 at 8:13 am
A new study shows that rapamycin, an immunosuppressive drug used in some cancers, and its analogs, may have an undesirable effect on viral entry into the host cells. This finding could inform their ...
- One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiencyon April 18, 2021 at 5:00 pm
To assess olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children. Methods. This ...
- Starving tuberculosis of sugars may be a new way to fight iton April 15, 2021 at 7:12 am
Tuberculosis is a devastating disease that claims over 1.5 million lives each year. The increase in TB cases that are resistant to the current antibiotics means that novel drugs to kill Mycobacterium ...
- Oxford-AstraZeneca COVID vaccine induces cell spikes similar to SARS-CoV-2'son April 8, 2021 at 10:03 pm
The S1 subunit helps bind the virus to the angiotensin-converting enzyme 2 (ACE2), and the S2 subunit helps with membrane fusion with the host cell. The virus spike protein is the main target of ...
Go deeper with Google Headlines on:
Targeting host enzymes to fight disease
