{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:31:29Z","timestamp":1784698289583,"version":"3.55.0"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"7","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,2,16]]},"abstract":"<jats:p>\n                    Selective pressures on viruses provide opportunities to establish target site specificity and mechanisms of antivirals. Enterovirus (EV)-A71 with resistant mutations in the stem loop (SL) II internal ribosome entry site (IRES) (SLII\n                    <jats:sup>resist<\/jats:sup>\n                    ) were selected at low doses of the antiviral dimethylamiloride (DMA)-135. The EV-A71 mutants were resistant to DMA-135 at concentrations that inhibit replication of wild-type virus. EV-A71 IRES structures harboring resistant mutations induced efficient expression of Luciferase messenger RNA in the presence of noncytotoxic doses of DMA-135. Nuclear magnetic resonance indicates that the mutations change the structure of SLII at the binding site of DMA-135 and at the surface recognized by the host protein AU-rich element\/poly(U)-binding\/degradation factor 1 (AUF1). Biophysical studies of complexes formed between AUF1, DMA-135, and either SLII or SLII\n                    <jats:sup>resist<\/jats:sup>\n                    show that DMA-135 stabilizes a ternary complex with AUF1-SLII but not AUF1-SLII\n                    <jats:sup>resist<\/jats:sup>\n                    . This work demonstrates how viral evolution elucidates the (DMA-135)\u2013RNA binding site specificity in cells and provides insights into the viral pathways inhibited by the antiviral.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adg3060","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T13:59:17Z","timestamp":1708091957000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Enterovirus evolution reveals the mechanism of an RNA-targeted antiviral and determinants of viral replication"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-4536","authenticated-orcid":true,"given":"Jesse","family":"Davila-Calderon","sequence":"first","affiliation":[{"name":"Department of Chemistry, Case Western Reserve University, Cleveland, OH, 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