Corona virus shown: If a spherical shaped virus is prevented from changing to an hourglass shape, it can't fuse to a healthy cell and infect it.
Photo Credit: Beth Fischer/U.S. National Institute for Allergy and Infectious Diseases

Canadian research finds new pathway to attack viruses

In the western Canadian city of Edmonton, a recent research effort at the University of Alberta, in collaboration with other researchers at McMaster University in Hamilton Ontario, and in Russia, may lead to new ways to combat viruses.

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Dr Luis Schang, University of Alberta, has co-developed a new way to target viruses and inhibit infections © U of Alberta

In their effort to test reaction of viruses to molecules of drugs, the research by  Luis Schang and his team in the Faculty of Dentistry and Medicine,  including Dr. Mireille St Vincent and Ms. Che C Colpitts, discovered a new pathway and have created an entirely new way of attacking viruses.

For a virus to infect a cell, the virus has to change from a spherical shape to an hourglass shape. The new drug developed by Dr Schang and his team inserts itself into the virus and prevents it from changing to the necessary shape to fuse itself to a cell.

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While researchers had known for many years about the need for viruses to change shape to fuse to cells, no-one had previously looked into the bio-physics aspect of fighting viruses.

Traditionally, research and anti-viral drugs have focused on targetting the proteins and enzyme activity of viruses. By targeting the enzymic activity, the anti-viral drugs attempt to interrupt the replication of the virus.

Dr Schang and fellow researchers approached the issue from the biophysics aspect and by targeting lipids.

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Cells were infected with 10-fold dilutions of herpes virus treated (left two columns) or not (right two columns) with the lead research compound, aUY11, from less than one infectious particle (bottom right purple circles), 5, 50, 500, 5,000, or 50,000 infectious particles (middle and upper right circles, bottom, middle and top purple circles respectively). Live cells are stained in blue, dead cells do not stain and show in very light blue to white. The cells infected with 5,000 or 50,000 untreated infectious particles were entirely or almost entirely killed by the virus and therefore the circles show basically whitish. Cells infected with 5, 50 or 500 untreated infectious particles are mostly alive, except for the clusters of cells that were infected and killed by the virus. Cells infected with treated virus were not killed. © courtesy: Dr L Schang- U of Alberta

 

They began by testing synthetic copies of portions of known natural anti-viral lipids.

They first discovered that the synthetic structure had similar effects on the virus as did natural lipid molecules.  Then they found that certain molecules inhibited the virus from being able to change its own structure to the correct shape needed to fuse to a cell.  Without the ability to change to the correct shape, no infection can occur.

“The compounds or drugs we developed insert themselves inside a certain part of the virus and then the virus no longer has enough energy to change its shape and fuse to cells. When a virus fuses to a cell, this allows the virus to enter the cell and infect it,” explains Dr Schang. “So our discovery prevents the virus from infecting new cells, although it does not stop the virus from killing already infected cells.”

There are two general types of virus structure, one with no outside membrane, and one with.  So far, the research deals with the types of virus that have an outside membrane such as the herpes virus, influenza, SARS, hepatitis B and C, West Nile and Corona virus amongst others.

Dr Schang says, “No one had considered looking at this area, at lipids, as drug targets before. And no one had considered biophysics important for antiviral drug design and development. The target is new, and the way we designed the drug is totally different and new

With this new pathway to attack viruses and the ability to synthetically replicate the drug,  the team is continuing tests on lab models and also working on pre-clinical development with Pro-Physis, a bio-tech startup spun off from the University of Alberta.

Dr Schang notes that for such important research to take place, multi-disciplinary and national and international collaboration involving a variety of experts is often required. He says Dr. Vladimir Koshun and Dr. Alexey Ustinov were the chemist collaborators in the Russian Academy of Sciences, Moscow, Russia  who developed the test molecules and synthesized all the compounds and designed or co-designed many of them.
He points out that Drs. Raquel and Richard Epand, at McMaster University in Hamilton Ontario were the biophysicists who provided all the evidence for the effects on curvature changes. Dr Schang says their expertise on the biophysics side was invaluable in solving the mechanism of action of these molecules.

 

Journal of Virology- abstract

 

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