Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors. (PubMed, Nat Microbiol) - Nov 5, 2025 - "Here we present the cryogenic electron microscopy structure of the HSV-1 HP apo-complex (3.8 Å), along with structures bound to pritelivir (3.2 Å) and amenamevir (3.2 Å)-two clinically active, chemically distinct HPIs. The potency of both inhibitors against HSV variants bearing mutations within the HPI binding pocket supports the high-resolution mapping of key molecular interactions while revealing residues that govern their antiviral spectrum against alphaherpesviruses. Our results provide important insight into the unique architecture of the HP complex and the mechanism of inhibition of HPIs, paving the way for the development of next-generation antivirals to treat herpesvirus infections."
Journal • Herpes Simplex • Infectious Disease
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Aesop Cho; Alexandre Mercier; Annapurna Sapre; Arabinda Nayak; Ariel Lewis-Ballester; Christopher Richards; Eric Lansdon; Jit Mukherjee; Lindsey May; Pui Yan Ho; Qing Yao; Roberto Mateo; Thomas Aeschbacher; Varsha Nair; Xinchao Yu
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