Herpes simplex virus cannot multiply without its helicase-primase complex, the molecular engine that unwinds and primes viral DNA for copying. A team led from Yokohama City University, with collaborators at the University of Tokyo, Osaka University and Japan's quantum science institutes, has determined the structure of this complex and explained, at atomic level, how antiherpesvirus drugs shut it down.
Combining experimental structural biology with computational analysis, the researchers resolved the complex into two modules and showed that both the viral DNA and an approved helicase-primase inhibitor bind to the helicase module. The structure makes clear how the drug obstructs the machinery that the virus depends upon for replication, converting an empirically useful medicine into a mechanistically understood one.
The work appears in Cell Chemical Biology. Because the helicase-primase complex is conserved across the herpesvirus family, the authors argue the structural insight could guide the design of next-generation antivirals effective not only against herpes simplex but against related viruses for which treatment options remain limited, a meaningful prospect given how widespread lifelong herpesvirus infections are.