Scientists identify COVID-19 protein using Australian Synchrotron

10 April 2020

The Australian Nuclear Science and Technology Organisation (ANSTO) said on 7 April that Monash University researchers had identified the structure of a protein in the COVID-19 virus, which could be used in screening potential therapeutic drugs.

The researchers determined the 3D-structure of a SARS-CoV-2 protein at atomic resolution using the macromolecular crystallography beamlines at the Australian Synchrotron.

The Australian Synchrotron, in Melbourne, Victoria, opened in 2007.

The 3GeV national synchrotron radiation facility, the largest particle accelerator in the Southern Hemisphere, supports the research needs of Australia's major universities, research centres, and businesses. In 2015, the Australian Government announced a 10-year, AUD520 million ($324m) investment in operations, through ANSTO.

The Nsp9 protein in SARS shares 97% of its sequence with its counterpart from COVID-19. The researchers cloned a version of the CoV-19 Nsp9 protein for the experiments. These structures, which were described in a paper published in the journal bioRxiv, could potentially be used in drug screening and in targeted experiments to disrupt the replication of the virus.

The COVID 19 virus only produces 27 or so proteins. Scientists are trying to understand how to prevent production of these proteins inside our cells.

Research Fellow Dr Dene Littler, within the laboratory of Prof Jamie Rossjohn from the Biomedicine Discovery Institute, Faculty of Medicine, Monash University, has been examining some of the lesser-understood proteins produced by SARS-CoV-2.

One of these, the non-structural protein 9 (Nsp9) is thought to have a role in RNA binding, and the related version of the protein in SARS is known to be important for replication of the viral genome.

Rossjohn said, “This represents the start of an accelerated programme of research within Monash that is aimed at developing new anti-viral treatments as well as understanding how the immune system combats this virus”.

"This will be part of a broad strategy by the world's scientists to develop entirely new drugs that are specifically targeted at corona viral proteins, blocking the virus’s ability to infect and reproduce in human cells,“ said Littler.

“Viruses such as those that cause the common cold haven’t had sufficient health implications before to warrant large scale drug research programmes. However, in the face of the current pandemic that has obviously changed and we are playing a fast-paced game of catch up”.

The Australian Synchrotron fast-tracked access to the microfocus crystallography beamline (MX2) for the COVID-19 related research.

Using the new ACRF detector on the MX2 beamline, it took approximately 18 seconds to acquire a data set, which was then used to quickly construct a crystal structure of Nsp9,” said principal scientist Dr Alan Riboldi-Tunnicliffe.

He added that MX2 has a powerful narrow beam, which enables researcher to focus on particular parts of a crystal and see crucial interactions, such as binding.

The Australian Synchrotron has kept the MX2 beamline operational in response to the COVID-19 crisis. Researchers can send samples to the Synchrotron and use the instrument remotely. The Synchrotron has received samples relating to CoVID-19 from Australia, Singapore and China.

Photo: Eleanor Campbell, Sukritee Bhaskar, Alan Riboldi-Tunnicliffe at the Australian Synchrotron gaining insights into the structure of  proteins  (Source: ANSTO)

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