Posted on 6 November 2020
Like products on a factory assembly line, all proteins pass through ‘quality control’ checkpoints where they are inspected before they are transported to their destination to carry out their functions. The researchers showed that some viruses could hijack this manufacturing and distribution process in the cell.
The virus can use the cell’s machinery to copy their DNA or RNA and produce the proteins they need to make copies of themselves and take-over their host.
Research demonstrated that viruses tend to harness a step in this process where sugar molecules coat newly assembled proteins. The team was able to develop inhibitors to block an enzyme that trims, checks, and modifies the sugar coating process, which can disrupt the viruses’ ability to hijack the pathway.
When tested in human cells, these inhibitors where shown to reduce infection in dengue fever.
Professor Gideon Davies, from the University of York’s Department of Chemistry, said: "The trimming process is a crucial quality control step and when it does not occur, proteins are marked for degradation. The enzyme we have identified represents a key target for broad spectrum drug development against certain viruses, as inhibitors will trigger the destruction of their proteins.
“Targeting the sugar coat of viruses is a really exciting route to novel antiviral agents, especially in these challenging times. We hope to be extending this concept to SARS-Cov2 in the near future"
The findings have been published in the journal, PNAS, and are an important step in developing broad-spectrum antiviral agents.
Professor Spencer Williams, from the School of Chemistry at the University of Melbourne, said: “One approach to treating viral infections is to make a new drug for each virus that comes along. But it is slow.
“An alternative and attractive approach is to make a drug against a human target that viruses need to replicate. The same drug can then be used and reused against many different viruses, even ones that have yet to emerge.”
Professor Davies said: “It has been fantastic to work with the Melbourne group, and with specialist virologists in Warwick and Oxford. It was a real team effort"