# Artemisia Extracts Suppress H1N1 Influenza A Virus Infection by Targeting Viral HA/NA Proteins and Modulating the TLR4/MyD88/NF-κB Signaling Axis

## TL;DR

Artemisia plant extracts can fight H1N1 flu by targeting virus proteins and reducing inflammation, suggesting potential natural treatments.

## Contribution

The study identifies Artemisia L. extracts as potential anti-H1N1 agents through targeting viral proteins and modulating immune pathways.

## Key findings

- Artemisia L. extracts inhibit H1N1 virus attachment and reduce viral protein levels in vitro.
- Quercetin and luteolin are key compounds with strong binding to influenza proteins.
- Extracts modulate TLR4/MyD88/NF-κB pathways to suppress inflammation and viral replication.

## Abstract

Background: Influenza A virus is an acute respiratory virus that spreads quickly, affects a broad range of populations, and can lead to many complications and mortality. Artemisia L. species are widely used in traditional medicine, but their antiviral potential against H1N1 remains uncertain. Methodology: Network pharmacology and molecular docking were used to computationally explore their potential function in this domain, and to investigate how their invasion mechanisms and adsorption occur. UPLC-MS/MS analysis identified the main components of the extracts. The anti-H1N1 mechanism of Artemisia L. extracts was studied in vitro. Results: Network pharmacology identified 95 key targets between Artemisia L. and IAV, with quercetin and luteolin as core active compounds. Molecular docking predicted strong binding affinities between these compounds and influenza virus proteins. UPLC-MS/MS analysis identified 75, 100, and 64 chemical components in ACBE, AALE, and ACTE, respectively, mainly flavonoids and terpenoids. Artemisia L. extracts exhibited both preventive and therapeutic effects against H1N1, reducing progeny virus NP mRNA and protein levels. In vitro experiments showed that higher concentrations of the extracts prevent virus attachment to MDCK cells by denaturing the HA protein. NA plays an essential role in progeny virus release. We found that a high concentration of ACTE can inhibit NA up to 85%, and ACBE showed a low inhibitory effect on NA. Conclusions: In terms of therapeutic effects, Artemisia L. extracts can regulate intracellular inflammatory factors via the TLR4/NF-κB/MyD88 signaling pathways and reduce the expression of IL-1β, IL-6, TNF-α, TLR4, NF-κB, p65, and MyD88 at the mRNA level, thereby inhibiting H1N1 virus replication. These results suggest that bioactive components in Artemisia L. extracts may inhibit H1N1, potentially leading to the development of natural-product-based anti-influenza agents.