Analysis reveals potential of the helicase-primase inhibitor ABI-5366 in treating herpes simplex virus infections, suggesting novel therapeutic avenues.
Helicase-primase is an interesting target for small molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors. Here we analyze the series of patent applications from Assembly Biosciences (published between 03/2024 and 03/2025) covering their drug candidate ABI-5366 together with additional data from poster presentations, press releases and company updates. This me-too approach on the old Bayer urea series is currently in clinical phase I (NCT06385327) and the modification is the bridging of the two urea nitrogens via an alkylene linkage. The chemical structure for 1,3-disubstituted tetrahydropyrimidin-2(1 H)-one derivative ABI-5366 is presented and its potential opportunities and limitations as a long-acting oral administration or injectable depot drug compared to other HPIs are discussed.
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Gege et al. (2025) studied this question.
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