HPI drugs block herpes by freezing its replication enzyme, new study shows.

Harvard Medical School researchers have revealed how helicase-primase inhibitors (HPIs) block herpes simplex virus (HSV) by locking the viral helicase-primase enzyme in place, preventing DNA unwinding and replication. Using cryo-electron microscopy and optical tweezers, scientists captured near-atomic images and real-time data showing the drugs disable the enzyme’s two key functions. The findings, published in Cell on December 29, 2025, explain the mechanism of HPIs currently in U.S. clinical trials and approved in Japan, offering a path to treat drug-resistant HSV, especially in immunocompromised patients. The research provides a foundation for improved therapies against HSV and other DNA viruses.