Broad-spectrum antiviral development of PI3K inhibitor compounds

Currently, we have very few approved antivirals or vaccines available for the many viral pathogens that threaten our health. For the few viruses where we do have approved antivirals available, we are facing increasing drug-resistance and constant viral evolution continues to create new challenges to ensure our vaccines and antivirals remain effective. Therefore, it is essential to develop new safe and effective antiviral therapies. We need to use our scientific tools and local expertise to develop our own therapeutic strategies to actively protect our own people. Additionally, we need broad-spectrum antivirals in our toolkit to use as a first line of defence against any emerging novel viruses to give us time to develop and test vaccines for prevention.  

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Principal Investigator
Dr Natalie Netzler, Dr Claire Wang, Professor Peter Shepherd
Waipapa Taumata Rau | University of Auckland
Public Contact
Kim Thomas
teniwhacomms@otago.ac.nz
Project Timeframe/Status
-
In Process

Whakarāpopoto Rangahau Summary of Research

Viral infections have posed a persistent threat to our health throughout history. The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted heavily on the world economy and health care systems, with millions of deaths recorded.

To make matters worse, there are many other serious viral pathogens including influenza, which can be transmitted through similar mechanisms and have overlapping clinical features with SARS-CoV-2. 

Due to a number of complex factors including systemic barriers, viral pandemics such as influenza have disproportionately impacted Māori and Pacific Peoples with estimated mortality rates over seven times higher for Māori compared to non-Māori during the 1918 influenza pandemic. 

Currently, we have very few approved antivirals or vaccines available for the many viral pathogens that threaten our health. For the few viruses where we do have approved antivirals available, we are facing increasing drug-resistance and constant viral evolution continues to create new challenges to ensure our vaccines and antivirals remain effective.

Therefore, it is essential to develop new safe and effective antiviral therapies. We need to use our scientific tools and local expertise to develop our own therapeutic strategies to actively protect our own people. Additionally, we need broad-spectrum antivirals in our toolkit to use as a first line of defence against any emerging novel viruses to give us time to develop and test vaccines for prevention. 

Our team has extensive experience and a long record of drug development from initial chemistry right through to human clinical trials. Therefore, this is a therapeutic innovation project that can build a platform to establish Aotearoa New Zealand-unique antiviral therapies against a wide range of viruses that can rapidly be clinically tested in humans.

Our project has Māori co-leadership and co-design and aims to develop safe and effective broad-spectrum antivirals to combat significant viral pathogens with pandemic potential such as SARS-CoV-2, influenza and future novel or re-emerging viral threats. 

This will help to protect against excess morbidity and mortality from viral diseases that impact on all our populations including Māori and Pacific Peoples in Aotearoa New Zealand and beyond. The fact that it has potential efficacy against a wide range of viruses means it also gives this country a way to react quickly potential viral pandemics now and in the future.

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Te Hiranga a Rangahau Research Impact

Viruses such as SARS-CoV-2, HSV, influenza and RSV are major health problems facing Aotearoa New Zealand. For some of these infections, vaccines can reduce the risk of getting sick, but many people will still become ill so there remains a need for antiviral drugs to treat affected people.

Antivirals could also be a first line of defence against any new viruses that emerge to buy us time to develop vaccines and other antiviral tools to save lives. One type of antiviral drugs specifically targets the virus itself (e.g., Paxlovid and remdesivir for SARS-CoV-2, acyclovir for HSV and oseltamivir for influenza) but viruses can rapidly develop resistance to these. Another class of drugs targets the processes inside human cells that the virus needs to use when it infects us. 

This class of drug also has the potential to be effective against a wide range of viruses and targeting antivirals in this way offers the possibility of developing broad spectrum antivirals. More importantly, it is harder for viruses to develop resistance to these. Using both types of antiviral drugs in combination would potentially be even more effective, both in treating the infection and in preventing resistance from arising. In our previous work developing anti-cancer drugs we developed drugs targeting an enzyme called PI 3-kinase.

This plays a crucial role in a process within human cells that we know viruses also need to successfully infect cells. This led the team to think these drugs might be useful as antiviral therapies. The team’s preliminary studies have shown it can indeed block the infection SARS-CoV-2, herpes simplex, influenza and other human viral pathogens. The current funding will allow the team to carry out the key follow-on studies to understand how these drugs achieve their antiviral effects and to see whether their efficacy can be improved by use in combination with the type of antivirals that target the virus itself. 

The results of these studies will guide which types of viral infection we would target in clinical trials. For the final plan we would hold consultation fono/hui within our Māori and Pacific communities and healthcare partners from within our networks to hear perspectives of users and to provide a platform for two-way dialogue before further clinical development (i.e., human trials) to ensure appropriate engagement, approach and uptake. We would also consult with infectious disease clinicians to discuss how these drugs could be used clinically.

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Te Niwha

Kairangahau Research Personnel

​​Dr Natalie Netzler
Waipapa Taumata Rau (University of Auckland) |
Virology Lead
Dr Claire Wang
Waipapa Taumata Rau (University of Auckland) |
Biology Lead
Professor Peter Shepherd
Waipapa Taumata Rau (University of Auckland) |
Drug Development Lead


LOCATION - Tāmaki Makaurau | Auckland