Fromthe start of the COVID-19 pandemic, our scientists have been supporting Australia’s response.They have conducted critical preclinical evaluations of leading vaccines[Link will open in a new window], studied SARS-CoV-2 on surfaces[Link will open in a new window] and utilised existing research to detect the virus in wastewater[Link will open in a new window] - all the while adapting to working through a pandemic[Link will open in a new window] themselves.
Now, with the vaccineroll-out underway, they are turning their attention to finding new COVID-19 treatments.
And while vaccines are the gold standard forcontrolling the pandemic, they alone can’t stop all COVID-19 infections.
COVID-19 affects more than just our lungs
At first, it was thought that SARS-CoV-2, the virus that causes COVID-19, was a disease of theairways andlungs. That could then lead to life-threatening respiratory symptoms.
As the pandemic progressed, it has become clear that the virus can affect multiple organs. Including neural and cardiac tissues, sometimes causing widespread and permanent damage.
And so far, there arefewmedications available to treat severe COVID-19. These includethe antiviral drug Remdesivir, the steroid Dexamethasone, and a few monoclonal antibody cocktails.
While vaccines do reduce the numbers of people experiencing severe symptomsand reduce transmission, we also need safe, effective and affordable treatmentsthat specifically target SARS-CoV-2.
COVID-19 treatment thatcaninhibit viral replication, reduce symptoms and prevent long-COVIDwill be essential for our COVID-safe future.
Rapid screening platform for new COVID-19 treatments
A multi-disciplinaryteam, being led byDr S. S. Vasan[Link will open in a new window]will be looking to repurpose drugs already approved for other diseases.
“A great strategy to find potential COVID-19 treatments is to repurpose drugs already approved for other diseases. However, the current methods to do this are expensive, time-consuming and not fit-for-purpose,” Dr Vasan said.
“We will be developing our screening platform with fourtypes of clinically-relevant human tissues – lower respiratory tract, lung, neural, and cardiac – chosen due to the nature of how SARS-CoV-2 infects people.
"We will be deriving some of these from stem cells,which are special human cellsthatcan develop into different cell types," he said.
Lastyear,scientists at our Australian Centre for Disease Preparedness (ACDP), showed howlab-grown airway cells[Link will open in a new window]havethe potential tostudy respiratory viruses such as Influenza A. They have sincepublished a paperthat extends this approach to SARS-CoV-2.
Perfecting the system
We will tailor the new multi-tissue screening tool for infections by SARS-CoV-2 and all its variants of concern. This could help fast-track drugs for phase 2-3 human clinical trials and minimise the need for animal trials.
Working with our manufacturing colleagues, we will scale-up the multi-tissue system using quality control standardisation and automation techniques.
Thenovel high-throughput system willthenbe ready torapidly screen existing drugs.
As a human cell-based technology, thepre-clinical trial results will more accurately mimic many of our own responsesto infections.
The team will identify the responsesthat characterise progression of the disease. And then measure the effectiveness of the candidates undergoing testing to reversediseaseeffects.
To do this they will be looking atsystems biology, a biomedical approach to understand the bigger picture. For example, our scientists recentlyidentifiedthe keychanges inmetabolites and lipids[Link will open in a new window] whenferretsare infected by SARS-CoV-2.
They will now be comparing these types of readouts withdata from humans and organoids.Such comparisons haveproven usefulin gaining insight into cellular pathways associated with SARS-CoV-2 replication and pathogenesis.
When might we see some results?
The project is currently getting underway. The team are hoping to evaluate threeTGA or FDAapproved drug candidatesfor suitability to progress to phase 2-3 human clinical trialswithin a year.It is a very ambitious timescale but that’s what our scientistsare hereto do.
The project called the ‘sySTEMsinitiative’, including collaborators from Barwon Health and the University of NSW, received $998,355.93 from the Australian Government’s Medical Research Future Fund (MRFF) matched by $736kfrom CSIRO.