A study of flavonoid inhibitors against Monkeypox H1 phosphatase
Year: 2025
Type: article
Abstract: Poxviruses regulate their replication cycle through host phosphorylation pathways, with dual-specific phosphatase H1(DUSP-H1) playing a key role in immune evasion by dephosphorylating STAT1 and inhibiting interferon(IFN) responses. Given its high conservation across orthopoxviruses, it represents a promising antiviral target. This study screened a flavonoid library against DUSP-H1 from monkeypox virus (mDUSP-H1) using a malachite green-based phosphatase assay, identifying Myricetin, (−)-Gallocatechin, Cupressuflavone, (−)-Epigallocatechin gallate, Baicalein, and Herbacetin as potent mDUSP-H1 inhibitors (IC50: 7.07–14.05 μM). Docking analysis revealed key hydrogen bonding interactions between 5,7-hydroxyl groups of the hydroxyflavone backbone and Asp79 and Arg116 of mDUSP-H1, respectively. Additional interactions with Ser23 via the 3’-hydroxyl group seems to enhance binding and effectively blocking the enzyme’s active site. These findings align with previous studies on tyrosine phosphatase inhibitors, supporting flavonoids as broad-spectrum viral phosphatase inhibitors. Further structural and pharmacokinetic studies will aid in developing optimised antiviral therapies against monkeypox, variola, and cowpox viruses.
Source: Figshare
Authors: Hwa Young Kim, Mi-Sun Kim, Dong Hae Shin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6902430103
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