New anti-viral drugs to combat herpes

NHMRC Ideas grant funds UOW researchers

Dr Gökhan Tolun and Distinguished Professor Antoine van Oijen, both from the School of Chemistry and Molecular Bioscience, Molecular Horizons and IHMRI, have been granted $636,368 from the National Health and Medical Research Council (NHMRC) over three years for their project, “Revealing the molecular mechanistic details of viral DNA recombination towards developing novel anti-viral drugs”.

“We are working on determining the 3D molecular structures of several herpes virus proteins, and dissecting the details of their reaction mechanisms,” said Dr Tolun.

Herpes is a serious public health issue. The human herpesviruses (HHV) infect a staggering number of individuals worldwide, and several of these viruses have been classified as oncogenic viruses, meaning they can increase an individual’s chances of developing cancer.

“Almost all of the human population lives with at least one life-long herpes virus infection, many without knowing it,” said Dr Tolun.

“These viruses live inside us like ticking time bombs that can cause serious conditions such as cancer, Bell’s palsy (facial paralysis), ocular diseases (leading cause of infectious blindness in the world), encephalitis (brain inflammation causing cerebral dysfunction), and multiple sclerosis. Therefore, developing better therapies against herpes viruses will have a wide impact.”

The research team will use cutting-edge methodologies such as cryo-electron microscopy and single-molecule experiments (EM and fluorescent imaging) to understand how the herpes virus proteins behave in DNA recombination. Knowing the structures of the herpes virus proteins will support the development of novel anti-viral drugs.

Currently, there is very little protein structure information available regarding viral recombinases. However with the new cryo-electron microscopes at the Molecular Horizons research institute recently opened at UOW, this no longer poses such a barrier to the research progress in this area.

“We have one of the best microscopes in the world at UOW – the Titan Krios G3 – which soon will be placed into the cryo-EM suite of the Molecular Horizons building, that is purpose-built to satisfy the strictest criteria for running such microscopes, making it one of the few such buildings in the world. Therefore, it has the potential to generate image data for reconstructing the structures of biological macromolecules at atomic resolutions, which means we can determine and examine such structures at the atomic level. Once we determine the structures of these viral proteins involved in a biochemical reaction called single-strand annealing (SSA) DNA recombination, further studies can be carried out towards developing novel antiviral drugs that can be used in treating herpes infections,” said Dr Tolun. 

Research to date

The team have so far have managed to establish the insect cell lines that will be used in overexpression of the viral proteins for purification, and planning to optimise the overexpression and purification of the viral proteins later this year. Additionally they are dealing with many new challenges of managing ‘big data’.

“Since I have moved to UOW from the National Institutes of Health in the US, I have been involved in building capacity at UOW for tackling this challenge. It is a multi-layer process, involving data storage in different places for different purposes. UOW has very recently passed the milestone of establishing a petabyte of storage. That is 1000 terabytes!,” said Dr Tolun.

The team also works in collaboration with the high-performance computational cluster facility (HPC) called MASSIVE located at Monash University in Melbourne. 

Why this type of Research Funding is critical

Dr Tolun is very passionate about his research area and wanted to stress the importance of increased scientific funding to build a better future for all – particularly for research into virus control and novel diseases like COVID-19.

“Despite the fact that science and engineering is what drives humanity into the future, science funding is in a dire state!"

 “We must do something to improve science funding for being able to build a better future for all humanity, you and your loved ones. When you get cancer or an infection, the treatments you receive are the results of research. When your grandparents, parents, or you are diagnosed with a neurogenerative disease such as Alzheimer’s, currently there is not much you can do but to watch things get worse until eventual death. Research can one day provide treatments for such conditions, just as it does for certain types of cancers or many infections. Same applies to many other currently untreatable medical conditions: only research can find treatments and cures for them!”