Discovery and Characterization of a Hydroxypyridone-3-carboxamide Analog as an Antiviral Lead against Orthopoxviruses.

ABSTRACT: Orthopoxviruses remain a persistent global health concern due to the ongoing circulation of mpox, the possibility of the re-emergence of smallpox, and the threats posed by many poxviruses that infect animals and/or humans. The limited availability of antiviral drugs, the unproven efficacy in humans, and the emergence of resistant mutants underscore the need for new and better therapeutics. In this study, we identify and characterize ZW-2038, a hydroxypyridone-3-carboxamide analog, as an antiviral compound against vaccinia virus (VACV), monkeypox virus (MPXV), and cowpox virus (CPXV). Discovered through a focused in-house small-molecule screen, ZW-2038 exhibited low micromolar potency and high selectivity in primary human fibroblasts. The compound also reduced viral replication under physio

SUBMITTER: Pant A 

PROVIDER: S-EPMC12724559 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature