Herpes simplex virus (HSV-1) employs heparan sulfate (HS) as a receptor for cell attachment and entry. During late-stage infection, the virus induces human heparanase (Hpse) protein upregulation to remove cell surface HS, allowing viral spread. Researchers investigating various diseases are eager to find an effective heparanase inhibitor.
Researchers from the University of Illinois at Chicago, in collaboration with associates from the Universities of Georgia and the Netherlands’ Utrecht University, discovered a molecule that, when tested on human cells, effectively inhibited the herpes simplex virus’s heparanase activity and restricted the virus’ ability to spread. The molecule could be used in all kinds of diseases.
The cellular protein heparanase breaks down heparan sulfate, a molecule that makes up part of the structural framework of our cells. This mechanism is significant because it untangles many molecules entangled in cellular structures and is required for biological functions elsewhere in the body. The researchers compare this tightly controlled procedure to a “controlled demolition.”
However, when heparanase works improperly, it rapidly breaks down heparan sulfate, enhancing the spread of cancerous or viral cells released from the cellular framework.
Deepak Shukla, the Marion Schenk Esq. UIC’s Professor of Aging Eye Research said, “The expression shoots up, creating chaos. That’s what you need to block.”
Tejabhiram Yadavalli, a research assistant professor in ophthalmology and visual sciences at UIC and co-first author of the study, said, “But finding a molecule to do this safely has proven difficult.”
Heparanase is a crucial component of the cell’s pro-survival action; hence, blocking it can be harmful. When tested on cells, the newly discovered molecule turned out to be non-toxic. Additionally, heparanase inhibitors are frequently a type of anticoagulant heparin. A heparin-based compound was employed in the trial, but the researchers removed its anticoagulant characteristics, making it safe to use in that sense.
By testing the molecules on corneal cells, the scientists focused on how the molecules affected the herpes virus in the eye. A virus infection in the eye can cause ulcerative disease or possibly make a person blind. Herpes is a perfect virus for evaluating heparanase inhibitors because previous research by Shukla and his colleagues demonstrated heparanase’s crucial role in infections.
Yadavalli said, “While there is much research to be done before this molecule could be used in clinical treatments, the researchers say this is an important step in that direction. Once a nontoxic heparanase inhibitor is found for clinical use, it will save many people from a lot of hardship.”
Journal Reference:
- Dr. Pradeep cHopra, Dr. Tejabhiram Yadavalli, Francesco Palmieri et al. Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread. Angewandte Chemie. DOI: 10.1002/ange.202309838