Novel Method for Treating Herpesvirus Identified

A recent study out of University of Connecticut has identified a potential new approach for treating all 9 herpesviruses with one therapeutic. The study, published in mBio, demonstrated that targeting 2 metal ion-dependent enzymes of human herpesviruses with 2 compounds, AK-157 and AK-166, can inhibit the replication of the virus.

“A lot of people know the herpes simplex viruses, but there is actually a family of 9 different herpesviruses including cytomegalovirus (CMV) which causes a lot of problems for immunocompromised people, folks getting transplants and chemotherapy patients for example. We need better therapeutic agents that can be used in these very vulnerable populations,” says co-author of the study Dennis Wright, Ph.D., professor of medicinal chemistry in the School of Pharmacy at the University of Connecticut. “Right now, the therapeutic agents that are out there aren’t terribly effective in terms of being able to treat all the viruses, and many of them have a significant dose-limiting toxicities and associated side effects." 

The majority of drug discovery efforts against herpesviruses has focused on nucleoside analogs that target viral DNA polymerases. But after identifying that herpesvirus enzymes require two magnesiums to replicate, the UConn team tested a panel of compounds—including HIV integrase inhibitors, the anti-influenza agent baloxavir, 3 natural products previously shown to exhibit anti-herpes simplex virus (HSV) activity, and two 8-hydroxyquinolones, AK-157 and AK-166—for the ability to inhibit specific 2 metal ion-dependent enzymes and herpesvirus replication.

While HIV integrase inhibitors have been reported to inhibit replication of herpesviruses, the researchers found the integrase inhibitors exhibited weak overall anti-HSV-1 activity.  They did, however, find that 8-hydroxyquinolones displayed strong antiviral activity against both HSV-1 and CMV and could inhibit 1 or more of the two metal-ion-dependent enzymes.