# Calycosin targets the MAPK-EGR1 signaling axis to inhibit enterovirus 71 replication in cells and human colonic organoids

Article · Liu Y, Wang J, Chen X, Wu M, Zhang X, Zhou YH

- Archive id: doi:10.1080/21505594.2026.2711500
- Published: 2026-08-05
- Venue: Virulence
- DOI: https://doi.org/10.1080/21505594.2026.2711500
- PMID: 42555528
- PMCID: PMC13449819
- Citations: 1
- Source URL: https://doi.org/10.1080/21505594.2026.2711500
- PDF: https://europepmc.org/articles/PMC13449819/pdf
- Provenance: europepmc

## Abstract

The downstream effectors that mediate the pro‑viral function of the MAPK pathway during enterovirus 71 (EV71) infection remain poorly defined. Here we show that early growth response 1 (EGR1) is independently regulated by each of the three classical MAPK branches including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), and serves as a common downstream target of these pathways to promote EV71 replication and virus-induced cell death. Furthermore, we found that the natural isoflavone calycosin (CA) from Astragalus membranaceus acts as a regulatory probe of the MAPK-EGR1 axis. CA suppresses EV71-induced expression and phosphorylation of ERK, p38, and JNK, as well as the subsequent upregulation of EGR1, thereby inhibiting both viral replication and virus-induced cell death in conventional cell lines and human colonic organoid infection models. This pro-viral axis is conserved among several enteroviruses, including coxsackievirus B3 and enterovirus D68, and CA exhibits broad-spectrum activity against multiple enteroviruses by targeting this axis. Collectively, our findings establish the MAPK‑EGR1 axis as a key host‑dependency node for EV71 and other enteroviruses, and identify CA as a valuable chemical probe for interrogating this axis. This work not only deepens our understanding of the interplay between enteroviruses such as EV71 and their host, but also provides a mechanistic basis for host‑directed antiviral strategies.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Organoids & Organ-on-Chip](https://space-kitty.com/topics/organoids)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.