{"id":"doi:10.1080/21505594.2026.2711500","kind":"article","title":"Calycosin targets the MAPK-EGR1 signaling axis to inhibit enterovirus 71 replication in cells and human colonic organoids","authors":["Liu Y","Wang J","Chen X","Wu M","Zhang X","Zhou YH"],"author_count":6,"year":2026,"published":"2026-08-05","venue":"Virulence","cited_by":1,"doi":"10.1080/21505594.2026.2711500","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1080/21505594.2026.2711500","archive_url":"https://space-kitty.com/papers/doi:10.1080/21505594.2026.2711500","updated":null,"pmid":"42555528","pmcid":"PMC13449819","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13449819/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Calycosin targets the MAPK-EGR1 signaling axis to inhibit enterovirus 71 replication in cells and human colonic organoids\" by Liu Y, Wang J, Chen X et al., https://doi.org/10.1080/21505594.2026.2711500, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"organoids","name":"Organoids & Organ-on-Chip","domain_slug":"biotech"}],"cited_in_dossiers":[]}