New Study Identifies Different Approach to Attack Herpesviruses

A recent study demonstrated that targeting 2 metal ion-dependent enzymes of human herpesviruses with 2 compounds, AK-157 and AK-166, can stop the replication of the virus, according to an American Society for Microbiology press release.

“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,” said study co-author Dennis Wright, PhD, professor of medicinal chemistry in the School of Pharmacy at the University of Connecticut, in the press release. “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."

Wright said that there would be 1 drug that could inhibit the reactivation of all 9 of the herpesviruses. According to co-study author Sandra K. Weller, PhD, there are herpesvirus enzymes that require 2 magnesium for the herpesvirus to replicate.

“The majority of drug discovery efforts against herpesviruses has focused on nucleoside analogs that target viral DNA polymerases. We are pursuing a strategy based on targeting two-metal-ion-dependent viral enzymes,” Weller said in the press release.

The researchers tested the ability of a panel of compounds to specifically inhibit 2 metal ion-dependent enzymes and herpesvirus replication in test tube studies. The compounds that were tested include HIV integrase inhibitors, the anti-influenza agent baloxavir, 3 natural products previously shown to exhibit anti-herpes simplex virus activity, and two 8-hydroxyquinolones, AK-157, and AK-166.

Although HIV integrase inhibitors have been reported to inhibit replication of herpesviruses, the research team found the integrase inhibitors exhibited weak overall anti-HSV-1 activity. However, 8-hydroxyquinoloses were found to display strong antiviral activity against both HSV-1 and CMV and could inhibit 1 or more of the 2-metal ion dependent enzymes, which opens an opportunity for researchers to potentially develop dual targeting agents against herpesviruses.

REFERENCE

Study identifies new way to attack herpesviruses. American Society for Microbiology. January 25, 2022. Accessed January 28, 2022. https://asm.org/Press-Releases/2022/Study-Identifies-New-Way-To-Attack-Herpesviruses