Image: Molecular model of the ACE2 Fc fusion protein structure. The ACE2 component is coloured Blue and green and the Fc red and purple.

Read an interview with Study Lead, Professor Mark Hogarth in IMPACT Spring 2020

Achievement

In a major development, our group’s COVID-19 program has created a set of biological medicines that completely inhibit the COVID-19 virus. We are now enhancing these “first generation” drugs by applying discoveries from our cancer and inflammation research to direct the immune system to kill the virus and the infection. We have made new discoveries that enhance the action of these biological drugs that make this possible.

These biological drugs neutralise the virus to prevent infection and also stimulate the immune system to destroy the virus and the cells infected by the virus to treat COVID-19 disease.

The problem

The rapid and uncontrolled spread of COVID-19 disease across the globe has exposed the complete lack of effective preventative or therapeutic interventions to control its spread. We have responded rapidly by developing biological medicines that can prevent and treat COVID-19.

Why is our approach unique?

To create our next-generation enhanced COVID-19 medicines, we are applying our pioneering discoveries from anti-cancer and anti-inflammatory biological medicines to make our COVID-19 medicines up to 100 times more powerful.

Image: 3-dimensional X-ray structure of an antibody. The Fab- fragments are coloured translucent grey and the FC portion is blue red.

How do the biological drugs work?

These medicines fall into two types called fusion proteins and monoclonal antibodies (mAbs).

1) Fusion proteins. Our first biological medicine is a fusion protein called ACE2-Fc. This has been created from two naturally occurring but separate components. The first component is the human receptor for the virus called ACE2. The second component is part of antibodies, called the Fc, that normally activates the immune system. By combining these two functions into one biological we can both prevent and also treat COVID19. This “two-pronged” attack on the virus is possible because of the following reasons.

Preventative (prophylaxis). The ACE2 component protects healthy people because it neutralises the virus and prevents it entering cells where it would otherwise establish infection.

Treatment (Therapeutic). The Fc component treats the infection by harnessing the normal immune system of the patient to kill the virus in infected people.

2) Monoclonal antibodies. Antibodies are produced naturally in response to infection and are individually isolated from people recovering from COVID-19 disease to create monoclonal antibodies by our Doherty collaborators.

Such monoclonal antibodies can act similarly to the ACE2-Fc and may neutralise the virus and activate the immune system. This monoclonal antibody technology has revolutionised cancer therapy so now we are applying and enhancing it for COVID-19 by enhancing their effectiveness against virus.

Thus, our biological medicines protect the vulnerable such as the frontline workers and family members of infected persons and will also treat those who develop the disease.

What are the broader applications?

An additional major benefit is that our ACE2-Fc medicine future-proofs the community against similar CoV threats in the future. If our medicine had existed at the start of the COVID19 pandemic it could have been immediately rolled out as a preventative medicine to stop the spread of the virus.