Virulence · Published 2026-08-05 · DOI 10.1080/21505594.2026.2711500
Yue Liu, Jiale Wang, Xin Chen, Mengli Wu, Xiangqian Zhang, Yan-Heng Zhou
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 from DOAJ. Public domain (CC0 1.0).
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Liu, Y., Wang, J., Chen, X., et al. (2026). Calycosin targets the MAPK-EGR1 signaling axis to inhibit enterovirus 71 replication in cells and human colonic organoids. Virulence. https://doi.org/10.1080/21505594.2026.2711500