Antiviral drugs: a biological defence against COVID-19
Professor Wai-Hong Tham from WEHI (Walter and Eliza Hall Institute of Medical Research) leads the consortium’s research. They are developing synthetic antibodies as antiviral drugs for COVID-19.
Synthetic antibodies can help prevent and treat viral infections, Wai-Hong says. These artificial antibodies act like our biological antibodies in the immune system. They defend the body against disease.
When a virus enters the body, it tries to bind to cells. This allows the virus to enter the cell. It then uses the cell’s machinery to reproduce and infect other cells.
One of the ways that antibodies prevent infection is by finding the virus and binding to it. This blocks the virus from binding to our cells and infecting them.
The role of antivirals
The COVID-19 pandemic in Australia was largely controlled by vaccination. But antivirals play an important role for vulnerable members of our community.
‘When someone has a vaccination, it triggers their body to develop its own antibodies to control the infection,’ Wai Hong says. ‘But this takes about 10-14 days to occur.
‘Immunocompromised people and the elderly do not always respond well to vaccination. But antivirals can give them immediate protection because they contain synthetic antibodies.
‘For this reason, antivirals can prevent disease. They can control an outbreak and stop it from spreading.’
Discovering an antibody to block SARS-CoV-2
COVID-19 is caused by the coronavirus known as SARS-CoV-2.
The coronavirus uses spike proteins to bind to our cells. These spike proteins protrude from the virus surface like a corona or crown, which is how the virus got its name. The spike proteins bind to the ACE2 protein on the outside of some cells.
To block the SARS-CoV-2 coronavirus from entering cells, the researchers needed to find an antibody that would bind to the coronavirus spike proteins. This would prevent the virus from binding with the ACE2 protein on cells.
Collaboration not competition
The researchers decided collaboration would give them the best chance of finding the most potent antibody.
‘We looked at the Australian landscape and realised that our academic and industry partners could bring together 5 different antibody platforms,’ Wai-Hong says.
Each platform has a different antibody library and unique analytic tools to compare antibody functions. The libraries include human antibodies from people who have recovered from COVID-19, small antibodies from alpacas, and synthetic antibodies created in the laboratory.
‘Testing possible antibodies on all 5 platforms head-to-head gives us the best chance of finding an antibody that will be effective against COVID-19,’ Wai-Hong says.
Screening antibodies in biosecure laboratories
The researchers screened the antibodies to find any that could bind with the coronavirus spike protein. Using biosecure laboratories, they tested the antibodies for their ability to block virus entry. The biosecure laboratories also allowed them to test the antibodies on mouse models of infection.
Using structural biology, the researchers obtained near atomic resolution images showing where the antibodies bound with the spike protein. This allowed them to compare and rank the best antibodies that block virus entry.
The challenge of new COVID-19 variants
When new COVID-19 variants emerge, the spike protein can change how it binds to antibodies. This occurred with the Omicron variant, Wai-Hong explains.
‘Unfortunately, many of the antivirals on the market were not effective against the Omicron spike protein,’ she says.
‘Using the 5 antibody platforms enabled our research program to quickly respond to Omicron,’ Wai-Hong notes. ‘We discovered new antibodies that work against this variant. We will continue to identify antibodies that work across all variants.’
Wai-Hong’s consortium aims to manufacture their new Omicron-blocking antibody and begin clinical trials in 2023.
Australian antivirals for future pandemics
International supply chain issues during the COVID-19 pandemic showed it is important for Australians to be able to manufacture our own medicines.
Wai-Hong’s research is helping to grow Australia’s ability to discover, test, and manufacture antiviral drugs.
The Medical Research Future Fund supported the project, Biologics for the prophylaxis and treatment of COVID-19, with a grant of $7 million.
Photo: Atomic scale image of synthetic antibodies (red) binding with SARS-CoV-2 spike proteins (blue).