Scientists find abandoned drug effective against two human viruses

By Ryan Whitwam 

While antibiotics have given humanity a powerful tool to fight pathogenic bacteria, viruses have proven a much more stubborn enemy. Vaccination has proven effective for many diseases, but they are harder to produce and usually must be administered in advance of infection. Researchers at Stanford have identified a previously abandoned drug that might shut down the ability of some viruses to infect cells and reproduce. There is hope this drug could help fight some of the most serious public health threats today including ebola, dengue, and zika.

Viruses are notoriously hard to fight largely because of their simplicity. Most of them are protein shells with a few receptors filled with genetic material. All they do is infiltrate cells, make more genetic material, and repeat. Even when we can develop vaccines, some viruses mutate so quickly that you won’t be protected for long (eg. influenza). This approach of focusing on a single virus at a time does yield results, but a drug that could combat many of them (more akin to antibiotics) would be ideal.

The Stanford team was made aware of a molecule that was studied at GlaxoSmithKline some years ago. It seemed to have good efficacy against a number of RNA viruses, but it was shelved. This is important because many of the dangerous viruses that are keeping medical staff busy are RNA-based — that is, they store their genetic information as RNA rather than DNA like most organisms do. When tested in human cell cultures, this as-yet unnamed drug is able to protect cells from Venezuelan equine encephalitis virus (VEEV) and dengue, both of which usually kill the cells. However, it also affected the human cells’ ability to divide.

To understand what the drug was doing, the team had to figure out what molecule it was inhibiting. Using advanced genetic screening techniques, they learned that the drug blocks the activity of a protein that is crucial for generating building blocks of RNA. That explains why the viruses were unable to replicate and kill the human cells, but it also helped the researchers devise some possible solutions to the side effects.

The same genetic building blocks that are needed for RNA synthesis are needed for DNA synthesis. So, it makes sense that the human cells in culture would be unable to divide — they can’t replicate their genome for the new cell. To compensate, the team supplied cells with different precursors that could be used to make DNA, but not RNA. This effectively shuts the virus out from being able to create more copies of itself, while allowing the human cell to divide normally.

The team is careful to point out this has only been shown to work in vitro. Giving this drug to a live person is still a long way off. Our cells use RNA in various ways as well, so there could be long-term issues from this drug. However, the side effects might be mild, and we are talking about life-threatening diseases. The risk might be worth it.