Supplied Professor Frederick West from the University of Alberta’s chemistry department thinks it’s a “happy coincidence” that brought him and professor David Marchant from the faculty of medicine together to develop a new promising antiviral compound.
The work by West and his collaborators, which was published in April in The Journal of Organic Chemistry, demonstrated the compound had antiviral properties against respiratory syncytial virus (RSV) and Zika in cellular culture. Both viruses currently have no vaccine or effective antiviral treatment.
The project began when Bren Jordan Atienza, a recent chemistry PhD graduate from West’s laboratory, was working on a chemical reaction unrelated to therapeutics. He noticed he was producing compounds structurally similar to isatisine A, which is known to be mildly antiviral. This prompted Atienza to suggest testing the compounds for antiviral properties.
West then reached out to the university’s Li Ka Shing Institute of Virology. Marchant, an RSV researcher who had been actively looking for new drugs, found some of the compounds prevented infection in cellular culture. The compounds also inhibited Zika infection, as demonstrated by Tom Hobman, a professor from the faculty of medicine.
The group then went through multiple stages of testing to improve the compound’s antiviral properties before publishing their work.
They also demonstrated the compound works by inhibiting RSV polymerase, the enzyme responsible for copying the virus’ genetic information, thereby preventing the virus from replicating and spreading.
“If you want to understand how to have the best possible drug, you really need to know what it’s doing on a molecular level inside the cell, and we have a pretty good idea of what’s happening,” West said.
RSV infects millions worldwide and while symptoms usually present only as a cold, complications can be fatal and cause roughly 200,000 deaths per year. Previous research shows most children under two in North America are infected at some point. Two per cent of these cases result in severe complications requiring hospitalization and costing the Canadian health care system $100 million per year.
As opposed to RSV, Zika is a mosquito-borne disease and is mostly restricted to tropical areas. Infection can cause fever, rash, and joint pain, and birth defects such as microcephaly in infected pregnant women.
Roughly 400 cases of Zika infection have been reported in Canada, and although most of them are travel related, West thinks the virus can pose a larger threat to Canadians.
“We don’t know what’s going to happen in the future with [climate] change… the mosquitoes that carry the disease could move north,” West said.
The compound will now be filed for a provisional patent application that an Edmonton company will potentially develop into a drug. However, West said this process will take at least 10 years of chemical, toxicology, and biological research and testing.
“This is an exciting project that everybody sees a lot of promise in that never would’ve happened without two very different labs coming together and bringing complementary expertise and backgrounds to the problem,” West said.
