New thinking: changing tack in the fight against viral infections

As the coronavirus pandemic highlights our deep vulnerability to novel viruses, researchers are bringing new ways of thinking to the development of desperately needed anti-viral treatments.

When it comes to our understanding of infectious disease, we’ve come a long way since the days when our medieval ancestors were strapping live chickens around swollen lymph nodes to try and cure the plague.

Yet our knowledge of how infectious diseases interact with our bodies remains patchy and, with drug resistance increasing, our treatment options continue to narrow.

One of the most pressing global health issues is our lack of treatment options to fight viruses – from emerging viruses like COVID-19 to well-known viral pathogens like dengue fever or zika virus.

“We have very few interventions against viruses,” says RMIT’s Dr Natalie Borg.

“We have around a dozen anti-virals against well-known infections caused by HIV, hepatitis C and influenza, and a wider range of vaccines.

“But for the vast majority of viruses we have absolutely nothing in terms of therapeutics. We can try to treat the symptoms, but we can’t deal with the actual disease.”

Viral infection is a major cause of death and economic burden globally, as the coronavirus pandemic has starkly illustrated.

But we lack serious investment in research to better understand viruses and develop new treatments, Borg says.

“Zoonotic viruses like COVID-19, which are transmitted between animals and humans, are emerging more often as we have closer contact with animals,” she says.

Modern humans also live more closely together and can travel vast distances easily, so viruses and infections spread more rapidly through the community and around the world.

“This is why it’s so crucial that we invest in developing new anti-virals and explore new ways of thinking to outsmart viruses as they mutate and evolve.”

Nurse in protective personal equipment, testing a patient's temperature

Viral infection is a major cause of death and economic burden, as highlighted by the COVID-19 pandemic.

A different approach

Borg heads the Immunity and Immune Evasion Laboratory at RMIT, part of the Chronic Inflammatory and Infectious Diseases research program in the School of Health and Biomedical Sciences.

Viral pathogens are a key focus for the team, with their work spanning basic research to understand the fundamentals of viral infection to translating new knowledge into clinical treatments.

Anti-viral treatments that target viral proteins are prone to resistance and failure over time, as viruses adapt and mutate.

So the lab takes a different approach, avoiding the problem of drug resistance by looking instead at proteins in the human body that viruses exploit.

“A virus needs the protein machinery in our cells to replicate and survive,” Borg says.

“Their viral proteins target ours. We want to understand which ones they hijack, which ones they block and which ones are essential to virus survival.

“If a particular human protein turns out to be essential to the life cycle of a virus, you can try to temporarily block it from working, so the virus can’t use it anymore – and that means it can’t survive.”

Outwit and outlast

Viral proteins use various tricks to enter our cells, hijack our cell machinery and outwit our immune system.

They can hijack our proteins to help themselves enter our cells, replicate and survive; hide from the proteins in our body that would flag them as threats, to raise an immune response; and lock the action of proteins that would trigger direct action by our immune system.

Any single virus will have a range of weapons in its armory. COVID-19, for example, has a large genome that encodes multiple proteins that work in a concerted effort to enable the virus to replicate.

“We can’t target every one of those weapons so we’re always searching for the Achilles’ heel of a virus, the key proteins that are vital to their survival,” Borg says.

Dr Natalie Borg

To deeply understand proteins and their interactions, the team works with techniques like X-ray crystallography, using X-rays from the Australian Synchrotron, to reveal precisely how viral proteins interact with our own proteins.

The lab is currently working to translate its research insights about human proteins into the development of new anti-viral treatments.

For Borg, who completed her undergraduate degree in Applied Biology/Biotechnology at RMIT, the human body and all its mysteries remain endlessly fascinating.

“There’s so much to be learnt, so many unanswered questions,” she says.

Story: Gosia Kaszubska

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13 May 2020

13 May 2020

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New thinking: changing tack in the fight against viral infections