Researchers have uncovered a surprise finding regarding treatment for the herpes simplex virus type 1 (HSV-1) — one that could open the door for new ways to fight the pathogen.
Scientists from the University of Illinois at Chicago (UIC) discovered that a drug molecule that typically promotes infection actually suppressed HSV-1 infection in corneal cells.
The experiment was conducted on corneal cells infected with HSV-1, commonly known as oral herpes.
The cornea is crucial when it comes to HSV-1. An untreated infection can lead to damage to the clear corneal tissue in the eye.
Over time, this can lead to the formation of ulcers that can cause severe pain, scarring, and even blindness.
Researchers studied BX795, a drug compound that’s known to prevent an enzyme called TBK1 from flourishing.
“TBK1 is important for antiviral activities by cells,” Deepak Shukla, a professor of ophthalmology as well as microbiology and immunology at the UIC College of Medicine and corresponding author on the paper, told Healthline.
“It’s part of innate immunity. And this compound, BX795, is actually a TBK1 inhibitor, so our original hypothesis was that if we blocked TBK1 — which is supposed to be antiviral — we should be allowing the virus to grow better,” he explained. “So obviously, if you try to block TBK1, one would expect the virus to do better. We didn’t see that happening, and we repeated experiments multiple times. Every time we used this inhibitor, the virus was getting suppressed instead of doing better. The entire discovery is a surprise to us.”
The researchers found that higher concentrations of BX795 led, somewhat counterintuitively, to infection being suppressed rather than promoted.
Treating a common infection
HSV-1 is one of the most pervasive pathogens affecting humans.
It’s estimated that between 50 and 90 percent of people worldwide have HSV-1, although many of them don’t show symptoms.
The infection lasts for life. This means that symptoms, including cold sores and corneal damage, can flare up throughout one’s lifetime.
The latest research is potentially big news when it comes to HSV-1. There aren’t many drugs approved to treat the virus.
“There are drugs to treat infection, and they belong to one single class of drugs: nucleoside analogue,” explained Shukla. “The drugs work and there are two drugs currently approved for topical treatment, but the problem is that there are a lot of cases of resistance. Once there’s resistance, you then have to give more and more of the same drug, higher quantities, or try to look for some other drug. Currently, there’s no other major class of drugs that’s available to treat herpes.”
When high quantities of nucleoside analogues are used to treat an HSV-1 infection, unwanted side effects can occur. This includes localized damage, such as glaucoma, because of changes to ocular pressure. There’s also the danger of toxicity, which can lead to long-term kidney damage.
“I think, in that regard, that our accidental discovery is important because it acts on a different protein,” said Shukla. “With our discovery, it’s technically a brand-new class of antiviral which could potentially be used to treat herpes.”
Potential applications go beyond herpes
Having found success testing BX795’s suppressive effect on both mouse and human corneal cells, the Chicago team hopes to attempt a clinical trial in the near future.
“My hope is that in the future, our drug can be given topically and nucleoside analogues and be given systemically, and together I think they will be effective and reduce the duration of treatment as well as the duration of disease,” said Shukla. “I think it opens up a totally new avenue.”
The next steps for Shukla and his colleagues involve developing systemic therapies, such as injectables and oral drugs, in addition to the topical treatment they’ve already tested.
There’s also the possibility that the treatment they’ve discovered could be applied to other viral infections, such as HSV-2, or genital herpes, and HIV.
“Since (BX795) acts on a host protein, I think there will be a broader-spectrum effect on several different viruses,” said Shukla. “There’s a potential for a broad-spectrum antiviral.”