High-Throughput Discovery of Inhibitors Targeting Monkeypox Virus H1 Phosphatase.

ABSTRACT: Mpox, caused by monkeypox virus (MPXV), remains a Public Health Emergency of International Concern (PHEIC) and poses a serious global health threat. Current therapeutic options for MPXV infection are limited. The orthopoxvirus dual-specificity phosphatase H1 plays critical roles in suppressing interferon signaling, regulating early viral transcription, and modulating viral core protease activity. Suppressing H1 expression markedly reduces the production of infectious viral particles, highlighting it as a promising antiviral target. Here, we developed a high-throughput enzymatic assay using p-nitrophenyl phosphate as a substrate to discover MPXV H1 inhibitors. We demonstrated that both the N-terminal helix α1, which mediates H1 dimerization, and the catalytic residue Cys110 are indispensabl

SUBMITTER: Tao C 

PROVIDER: S-EPMC12656849 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature