{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:36:25Z","timestamp":1792654585891,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study, the antiviral activity of gramine and 21 gramine derivatives against EV71 was investigated in cell-based assays. Eighteen derivatives displayed some degree of inhibitory effects against EV71, in that they could effectively inhibit virus-induced cytopathic effects (CPEs), but the anti-EV71 activity of the lead compound gramine was not observed. Studies on the preliminary modes of action showed that these compounds functioned by targeting the early stage of the EV71 lifecycle after viral entry, rather than inactivating the virus directly, inhibiting virus adsorption or affecting viral release from the cells. Among these derivatives, one (compound 4s) containing pyridine and benzothiazole units showed the most potency against EV71. Further studies demonstrated that derivative 4s could profoundly inhibit viral RNA replication, protein synthesis, and virus-induced apoptosis in RD cells. These results indicate that derivative 4s might be a feasible therapeutic agent against EV71 infection and that these gramine derivatives may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents.<\/jats:p>","DOI":"10.3390\/molecules19078949","type":"journal-article","created":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T11:23:16Z","timestamp":1403868196000},"page":"8949-8964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Discovery of Gramine Derivatives That Inhibit the Early Stage of EV71 Replication in Vitro"],"prefix":"10.3390","volume":"19","author":[{"given":"Yanhong","family":"Wei","sequence":"first","affiliation":[{"name":"College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiao","family":"Shi","sequence":"additional","affiliation":[{"name":"National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaimei","family":"Wang","sequence":"additional","affiliation":[{"name":"National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Liu","sequence":"additional","affiliation":[{"name":"National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyong","family":"Ke","sequence":"additional","affiliation":[{"name":"National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/infdis\/129.3.304","article-title":"An apparently new enterovirus isolated from patients with disease of the central nervous system","volume":"129","author":"Schmidt","year":"1974","journal-title":"J. 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