New Approach for Treating Herpes

In the journal Angewandte Chemie, a research team has now introduced a completely new approach for treating herpes. Their method is based on the inhibition of an enzyme that is needed for the release of newly formed virus particles from infected cells.

The majority of adults carry the instigator of herpes in their bodies because, once infected, herpes simplex Type 1 viruses (HSV-1) settle into nerve ganglia. They remain in the body throughout a person’s life, inactive most of the time. If the immune system is temporarily weakened, maybe by anxiety or stress, too much sunlight, hormonal fluctuations, or a cold, an outbreak may occur. This is annoying and painful but usually harmless. However, this is not always the case: in some immunocompromised individuals or newborns there can be severe and sometimes life-threatening consequences. Antiviral drugs can curb herpes infections but not fully vanquish them.

A team has now developed an alternative method for the treatment of herpes.

HSV-1 viruses dock to heparan sulfates, molecules that are made of many sugar (saccharide) units and are found in the extracellular matrix and plasma membranes of our cells. Once bound, the viruses can enter the cells. In the late stages of infection the virus causes the infected cells to increase production of heparanase, an enzyme involved in the remodeling of the extracellular matrix. It splits heparan sulfates off the surface of the cell — a prerequisite for the release of the viruses newly produced in the cell so that they can spread to other cells and tissues. The idea behind this project is to block the heparanase.

The team synthesized a series of oligosaccharides that have structures like those of heparan sulfates but are not split by the heparanase enzyme. Molecules made of six or eight saccharides strongly inhibit heparanase. By using complementary computer studies, the team was able to model the way these oligosaccharides are arranged in the enzyme’s binding cavity and determine which molecular interactions are responsible for the strong binding. Treatment of corneal cells infected with HSV-1 with the active oligosaccharides had the effect of inhibiting the virally induced excretion of heparan sulfates, significantly reducing the spread of the virus.

In addition, inhibition of heparanase through the new inhibitors can impede the migration and proliferation of immortalized cells (that is, cells with uncontrolled cell growth). This enzyme has been strongly implicated in cancer metastasis, suggesting another potential application for the inhibitors in the future.

Sources: 

Pradeep Chopra, Tejabhiram Yadavalli, Francesco Palmieri, Seino A. K. Jongkees, Luca Unione, Deepak Shukla, Geert‐Jan Boons. Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread. Angewandte Chemie International Edition, 2023; DOI: 10.1002/anie.202309838

Wiley. “Keeping herpes in check.” ScienceDaily. ScienceDaily, 7 September 2023. <www.sciencedaily.com/releases/2023/09/230907105827.htm>.

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