Malaria discovery could expedite antiviral treatment for COVID-19

Date:
August 11, 2020
Source:
RMIT University
Summary:
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.



FULL STORY ==========================================================================
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, not
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,
from 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 and Burnet Institute), Dr Jean- Philippe Semblat (from French Government agency
Inserm, Paris) and Prof Oliver Billker (Umeaa University, Sweden and
Sanger Centre, UK).


========================================================================== Story Source: Materials provided by RMIT_University. Original written
by Grace Taylor. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jack D. Adderley, Simona John von Freyend, Sarah A. Jackson,
Megan J.

Bird, Amy L. Burns, Burcu Anar, Tom Metcalf, Jean-Philippe Semblat,
Oliver Billker, Danny W. Wilson, Christian Doerig. Analysis of
erythrocyte signalling pathways during Plasmodium falciparum
infection identifies targets for host-directed antimalarial
intervention. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-17829-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200811120143.htm

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