A new research published this week in mBio, an open access publication of the American Society for Microbiology, has uncovered a novel way to combat herpesviruses. The research found that two chemicals, AK-157 and AK-166, may suppress the replication of human herpesviruses by targeting two metal ion-dependent enzymes. The discovery opens up new possibilities for producing anti-herpesvirus drugs.
“Many people are familiar with herpes simplex viruses, but there are really nine distinct herpesviruses, including cytomegalovirus (CMV), which may cause serious issues in immunocompromised persons, transplant recipients, and chemotherapy patients. Better therapeutic agents are needed for these very sensitive individuals “Dennis Wright, Ph.D., a co-author of the research and a professor of medicinal chemistry at the University of Connecticut School of Pharmacy, remarked “Right now, the treatment drugs that are available aren’t very successful in terms of treating all viruses, and many of them have major dose-limiting toxicities and side effects.”
According to Wright, the ideal medicine would be one that inhibited the reactivation of all nine herpesviruses. Sandra K. Weller, Ph.D., a renowned professor of molecular biology and biophysics at the University of Connecticut School of Medicine, found targets that might enable this. She discovered herpesvirus enzymes that need two magnesiums to propagate the virus. “Nucleoside analogs that target viral DNA polymerases have been the focus of most therapeutic development efforts against herpesviruses. We’re working on a method that focuses on viral enzymes that are reliant on two metal ions “Weller said.
The researchers used test tubes to see whether a panel of chemicals might suppress two metal ion-dependent enzymes as well as herpesvirus replication. HIV integrase inhibitors, the anti-influenza drug baloxavir, three natural products previously demonstrated to have anti-herpes simplex virus (HSV) action, and two 8-hydroxyquinolones, AK-157 and AK-166, were among the substances studied.
While HIV integrase inhibitors have been shown to reduce herpesvirus replication, the researchers discovered that the inhibitors had modest anti-HSV-1 effect overall. The researchers discovered that 8-hydroxyquinolones have potent antiviral action against HSV-1 and CMV, as well as the ability to block one or more of the two metal ion dependent enzymes. This opens the door to the development of dual-targeting agents against herpesviruses.