A research team led by Assistant Professor Hikaru Sato and Associate Professor Toru Sengoku at Yokohama City University determined the atomic structure of proteins required for simple herpes virus DNA replication. The group collaborated with Professor Osamu Nureki of the University of Tokyo, Professor Kaoru Fukuzawa of Osaka University, and Dr. Hidetoshi Kono of the National Institutes for Quantum Science and Technology (QST). The findings, published in Cell Chemical Biology, explain how specific drugs block the virus from multiplying.
Current herpes treatments face resistance and limited scope
Eight types of human herpes viruses cause conditions including simple herpes, chickenpox, and shingles. These infections can become severe in immunocompromised patients. Some recent reports also link these viruses to autoimmune diseases, and dementia.
Existing antiviral medications don’t work for every strain. Clinicians struggle with drug-resistant viruses and adverse side effects. These limitations create a need for treatments that target the virus more effectively.
How researchers mapped the viral protein structure
The team focused on the helicase-primase complex (HPC), a protein essential for DNA replication. They used cryo-electron microscopy to visualize how the HPC interacts with inhibitors. The HPC consists of two modules, and the study found that both the viral DNA and the drug amenamevir bind specifically to the helicase module.
The study examined two inhibitors, amenamevir and pritelivir. These drugs block the HPC’s function to stop the virus from multiplying. The researchers used computational chemistry to quantify the binding strength and verify the movement of the enzymes.
Toward the design of next-generation antivirals
This atomic-level map provides a structural basis for designing new medications. Researchers can now target the HPC more precisely to create drugs that work across various herpes virus types. Such developments could reduce the occurrence of resistance and improve outcomes for patients with severe infections.
What is the helicase-primase complex (HPC)?
The HPC is a protein complex that the herpes virus uses to replicate its own DNA.
Which drugs were analyzed in this study?
The study analyzed amenamevir, marketed as Amenalief, and pritelivir.