In 2014, at the height of the Ebola epidemic, UVA biologist Judith White and her colleagues began working on a way to fight that disease with a drug cocktail. They figured it should be possible to combine medications for various viral groups.
“With HIV and hepatitis C virus, there are anywhere between two and four drugs," she explains. "The basic concept is to hit the virus at different sites in the viral life cycle.”
By using more than one medication, they could possibly ward off two potential problems with drug treatment.
“It minimizes the chance of getting drug resistant mutants, and the other thing is you can lower the doses,” White says.
And they used a strategic approach – pairing or combining drugs based on several factors.
"It’s basically how potent they are at blocking the virus in a cell culture. What are the levels of the drug over time in your blood stream, in the lung. How quickly does it decay, which would impact how frequently you have to take the drug as well as what’s known about how the virus replicates," says White.
Unfortunately, their research was slowed by a lack of funding. As the risk of Ebola fell, so too did enthusiasm for this approach, but with the arrival of COVID, White and her collaborators began feeding key information into a computer, allowing them to develop models for crafting different drug cocktails for each viral family.
“There are 11 families of human viruses that are considered of pathogenic potential. If a new virus is suspected, we would know very quickly: Is it a coronavirus? Is it a filovirus? Is it a flavivirus? We would have on the shelf drug cocktails A, B, C, D, E so to speak, and we would know if it’s a flavivirus, cocktail C has a really good chance of working on it. The idea is to make these cocktails against the whole virus family.”
Ideally, Judith White says, generic drugs – already approved for use in humans, could be combined to treat new diseases.
"They’re very inexpensive, and they are room temperature stable. They don’t need to be frozen. They’re oral drugs, so it has much more global potential. They could be used in low and middle income countries. They could be easily shipped over there. You don’t need specialized, skilled clinical people to administer them, so we think of them as practical and thoughtful drug combinations for the whole world."
But for each virus family, she says, initial testing must be done on the right kind of cells.
"One issue with COVID in particular is when you do the work in the cells, you have to do it in a lung cell. + A lot of the early work + has been done in a cell line that’s not really relevant to COVID disease -- notably hydroxychloroquine, ivermectin. They don’t work in lung cells, and so they were really non-starters.”
What she’s doing now may not produce a cocktail in time to battle COVID, but White hopes their approach will prepare the world to fight future pandemics.
“The idea in terms of pandemic preparation is to really just tamp down the infection within an individual and within the population at the very earliest time after we know that something is brewing.”
For now, she says, the best bet for a world coping with COVID is to get vaccinated and, if necessary, to take recently approved medication designed to keep patients out of the hospital.
