ArticleInfection and drug resistance2026
Integrated UHPLC-QTOF-MS, Network Pharmacology, and Experimental Validation Reveal the Antiviral and Anti-Inflammatory Mechanisms of Xiaoer Fengreqing Against COVID-19-Associated Encephalitis.
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Abstract
Background: Xiaoer Fengreqing (XF), a traditional Chinese medicine, is included in pediatric COVID-19 guidelines, but its active components and mechanisms remain unclear. This study aimed to explore XF's bioactive constituents and potential effects against COVID-19-related encephalitis. Methods: UHPLC-QTOF-MS and network pharmacology were used to identify active compounds, targets, and pathways. Antiviral effects against Omicron were assessed by cytopathic inhibition assays. RT-qPCR and Western blot evaluated anti-inflammatory responses, and in vivo experiments tested antiviral and neuroprotective effects against HCoV-OC43 using an intracranial infection model. Results: UHPLC-QTOF-MS identified 220 compounds, with 137 absorbed into plasma, yielding 774 potential targets and 242 KEGG pathways. Core targets included ACE2, EGFR, PARP1, JAK1, and SRC. Molecular docking showed isoalantolactone and isosakuranetin interacted with ACE2. XF exhibited an IC Conclusion: XF may exert antiviral and neuroprotective effects against COVID-19-related encephalitis through TNF-α/IL-6 suppression and modulation of MAPK, JAK/STAT, and PI3K/AKT immune regulatory pathways. Although XF showed potential for further development, its clinical translation remains limited by the complexity of its components, the lack of evaluation of individual active compounds, and its relatively modest in vitro antiviral potency. Therefore, in the absence of clinical trial evidence, XF should be regarded only as a candidate for further investigation.
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