An extensive search and testing of current drugs and drug-like compounds has revealed compounds previously developed to fight SARS might also work against COVID-19.

Using the National Drug Discovery Centre, researchers from the Walter and Eliza Hall Institute of Medical Research (Parkville, Victoria, Australia) have identified drug-like compounds that could block a key coronavirus protein called PLpro.

This protein, found in all coronaviruses, is essential for the virus to hijack and multiply within human cells, and disable their anti-viral defenses. Initially developed as potential treatments for SARS, the compounds prevented the growth of the SARS-CoV-2 virus (which causes COVID-19) in the laboratory. PLpro belongs to a family of proteins called ‘deubiquitinases’, which the researchers had studied for the last 15 years in a range of diseases. They quickly established the VirDUB program to investigate how PLpro functions and what it looks like. Using ANSTO’s Australian Synchrotron, the VirDUB team rapidly ascertained how PLpro interacts with human proteins – homing in on a target that could be blocked by new drugs. The National Drug Discovery Centre proved critical to rapidly search for drugs that could block PLpro. The next step is to turn these compounds into drugs that could be used to treat COVID-19.

“We now need to develop the compounds into medicines, and make sure they are safe for patients,” said Professor David Komander who led the discovery. “Importantly, drugs that are able to inactivate PLpro may be useful not just for COVID-19 but may also work against other coronavirus diseases, as they emerge in the future.”

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Walter and Eliza Hall Institute of Medical Research