Closing the door on colds and flu

New research by scientists at the University of Toronto and the Structural Genomics Consortium has deepened our understanding of how viruses like the flu, common cold, and COVID-19 get into cells in human airways.

Using the Canadian Light Source at the University of Saskatchewan, the researchers identified for the first time the crystal structures of a human protein (TMPRSS11D) that viruses use as a doorway into our body.

Understanding how viruses use our proteins to gain entry into our cells will help researchers develop better ways to stop infections in their tracks.

“This paper is really the stepping stone for building out more effective antiviral agents,” says lead author Bryan Fraser, a University of Toronto postdoctoral researcher at the Structural Genomics Consortium.

“We’re using the structure-based information that we've gained here to guide us in improving molecules that we hope will become drug candidates.”

Knowing the crystal structure of this “doorway” protein, says Fraser, is key to finding helpful drugs to stop coronavirus and influenza viruses, because it is very similar to other important proteins in the human body.

“Many of the important proteins for coagulation that are present in your blood look a lot like the TMPRSS proteins,” Fraser explains.

Successfully drugging subtle features on the TMPRSS proteins that are not present in coagulation proteins can be the difference between stopping infections and interfering with how wounds heal.

“The major challenge in our field is finding really effective compounds or drug candidates that show they’re selective for the target you’re interested in, and don’t block those other essential functions,” says Fraser.

While precise targeting is a challenge, the promise of these proteins as drug targets is immense.

“It's really exciting that all the antiviral work we do against these targets may have potential impact for various influenzas and common cold viruses, as well as pandemic threat coronaviruses,” says Fraser.

By targeting these proteins, researchers develop many ways to reduce illness, including treatments for the sick, preventative medicines, and vaccines. Fraser and collaborators at the Université de Sherbrooke are already looking for the drugs that will make these treatments possible.

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Fraser, Bryan J., Ryan P. Wilson, Olzhas Ilyassov, Jackie Lac, Aiping Dong, Yen-Yen Li, Alma Seitova et al. "Structural basis of TMPRSS11D specificity and autocleavage activation." bioRxiv (2024): 2024-10. https://doi.org/10.1038/s41467-025-59677-3

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Greg Basky
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Canadian Light Source
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greg.basky@lightsource.ca