Researchers identify a pathway that filoviruses use to enter cells

Ebola and filoviruses were once thought to be largely associated in Central Africa. After the West African revolution and the discovery of Reston ebolavirus in the Philippines, cuevavirus in Spain and various bat filoviruses in China, researchers now understand that this viral family – causes fever hemorrhagic with case mortality rates of up to 90% – has been widespread worldwide for millions of years.

Our defense against it is more embryonic, and while we have a vaccine against one species of Ebola and some therapeutic antibodies on the horizon, both have production or circulation issues. What doctors have been hoping for is a regular drug that can treat Ebola as soon as it raises its scary head. A study published today in the journal Pathogens PLOS, identifies a pathway that each filovirus uses to enter our cells – and shows how they can block their pathways with at least one FDA – approved drug.

Ebola is so pernicious because it quickly draws a man on the body, hiding itself as a dying cell.

It encapsulates itself in a lipid that is not normally exposed at the cell surface. It is only open when the cell undergoes apoptosis. “

Dr. Marceline Côté, Principal Investigator and Associate Professor, Department of Biochemistry, Microbiology and Ornithology, Canadian Research Chair, Molecular Virology and Antiviral Medicine

Dr. Côté is a leading global expert on how viruses enter us, an understanding that is essential in any attempt to keep them out.

The malingering virus is then taken up by cells of the immune system that carry the virus to other parts of the body, spreading the infection. Almost all organs are going to be sites of active reproduction, and the result is a terrible, multisystem disease. As soon as it makes its way into the cell, the virus needs to find a specific receptor that acts as a lock for its glycoprotein key, starting the process that allows it to multiply. A drug that prevents it from taking a single step in turning that key on could cause the disease.

Dr. Côté’s team, in particular PhD student Corina Stewart, tested a library of antiviral drugs in cell cultures. It is not safe to work with Ebola replica virus in a regular laboratory, so the uOttawa team used a replacement system.

“We use a safe virus in question as an Ebola virus. They enter in exactly the same way as an Ebola virus, but in reality it is the inner heart when they cook all the ingredients. safe, “said Dr Coté. “It’s a murine leukemia virus or engineered retroviruses, so there’s nothing to worry about.”

As soon as they found a collection of drugs that appeared to be working, they passed the data to their colleague Dr. Darwyn Kobasa at the national microbiology laboratory in Winnipeg, where a level 4 biosecurity rating allows researchers to treat the bona fide virus. Dr. Kobasa confirmed that a small number of cancer chemotherapy drugs were effective in preventing Ebola from gaining a foothold in the cells.

While these types of drugs can be painful for the body, Ebola is a life-threatening disease. In addition, the disease does not last long, so unpleasant treatment can be the same short-lived.

It is also known which drugs worked against Ebola also tell the team more about how to get the virus. In particular, this study shows that Ebola virus has developed ways to be active in cell invasion. Previously, it was thought that viral infiltration was left largely by chance, with many grains left while a small number were randomly introduced into the cell. Dr. Côté’s study shows that the virus has evolved to get in very effectively, rather than just going on the trip.

“They are not passive travelers,” Dr. Côté said. “Their hands are on the steering wheel.”