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New Drug Class Developed for Herpes

Investigational small molecule drug may be able to treat herpes and HIV.
Published Online: Feb 20,2018
Laurie Toich, Associate Editor
There are only a few drugs on the market that can treat the painful symptoms of herpes simplex-1 virus (HSV-1). If patients develop resistance to current therapies, they have limited options for the rest of their life.

In an effort to better treat the symptoms of the virus, researchers recently discovered a new small molecule drug that demonstrated the ability to clear HSV-1 in cells of the cornea, according to a study published by Science Translational Medicine.

Perhaps the most notable finding was that the drug works completely different from current herpes drugs, meaning that it could be a viable option for patients with drug resistance.

The authors hypothesize the new therapy could treat HSV-1 of the mouth, HSV-2 of the genitals, and possibly HIV.

Up to 90% of the global population has HSV-1, which primarily affects the mouth and eyes. The virus is transmitted through bodily fluids and persists for the entirety of a person’s lifetime.

Oral and topical antivirals can temporarily eliminate the infection in the eye, but corneal inflammation requires consistent steroid-based eye drops. Patients may go on to develop blindness due to HSV-1.

Nucleoside analogs block HSV-1 from producing proteins needed for replication; however, these treatments can cause glaucoma and other serious adverse events.

“We have needed alternative drugs that work on new targets for a very long time because patients who develop resistance to nucleoside analogs have very few good options for treating their infection,” said corresponding author Deepak Shukla, PhD. “We have found a molecule that works in a totally novel fashion. Instead of working on the virus, it works in the host cells and helps them to clear the virus.”

The small molecule—BX795—was found to clear HSV-1 in human corneal cells, in donated human corneas, and corneas of mice with the infection, according to the study.

These findings were surprising because BX795 is an inhibitor of the TBK1 enzyme, which is involved with immunity and neuroinflammation, according to the authors.

Normally, TBK1 promotes infection when its inhibited; however, the infection subsided when the authors added a high concentration of BX795 to cultured corneal cells.

The same results were observed in human corneas and in mice models of HSV-1, according to the study.

“This isn’t what we expected,” said co-author Tejabhiram Yadavalli, PhD. “Instead of promoting infection, at higher concentrations, BX795 actually helped cells clear the infection.”

The authors also found that the concentration of the drug needed to clear the infection was low.

“We saw clearance of the virus at concentrations of BX795 that were five times lower than concentrations of antiviral compounds in available nucleoside analogs,” Dr Shukla said.

Another benefit to the novel drug was that it only affected infected cells, which may prevent widespread toxicity, according to the authors.

The researchers project that the treatment could be used to prevent replication for other viruses as well.

“Because BX795 targets a common pathway that many viruses use to replicate inside the cell, it could be a new kind of broad-spectrum antiviral that might be used to treat other viral infections, including HSV-2, which primarily affects the genitals, and HIV, although we have not yet tested it on viruses other than HSV-1,” Dr Shukla said.