{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:19:20Z","timestamp":1790677160125,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","award":["Legge Regionale 7 agosto 2007: CRP1_574"],"award-info":[{"award-number":["Legge Regionale 7 agosto 2007: CRP1_574"]}],"id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","award":["22\/41 del 2017, RASSR01499"],"award-info":[{"award-number":["22\/41 del 2017, RASSR01499"]}],"id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Autonomous Region of Sardinia, European Social Fund 2014-2020","award":["P.O.R. Sardegna F.S.E, Specific goal 10.5"],"award-info":[{"award-number":["P.O.R. Sardegna F.S.E, Specific goal 10.5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described theirin vitrocytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 \u00b5M. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 \u00b5M. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for furtherin vivoassays.<\/jats:p>","DOI":"10.3390\/v13010058","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T21:58:36Z","timestamp":1609797516000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Inhibition of Enterovirus A71 by a Novel 2-Phenyl-Benzimidazole Derivative"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-3845","authenticated-orcid":false,"given":"Roberta","family":"Ibba","sequence":"first","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, Via Muroni, 23A, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, Via Muroni, 23A, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-8329","authenticated-orcid":false,"given":"Silvia","family":"Madeddu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Monserrato (Cagliari), 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Caria","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Monserrato (Cagliari), 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-3989","authenticated-orcid":false,"given":"Gabriele","family":"Serreli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Monserrato (Cagliari), 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, Via Muroni, 23A, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-525X","authenticated-orcid":false,"given":"Simona","family":"Sestito","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, Via Muroni, 23A, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Loddo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Monserrato (Cagliari), 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3999-4263","authenticated-orcid":false,"given":"Giuseppina","family":"Sanna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Monserrato (Cagliari), 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6051","DOI":"10.3390\/v7112920","article-title":"Neurotropic Enterovirus Infections in the Central Nervous System","volume":"7","year":"2015","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S1474-4422(08)70207-2","article-title":"Enterovirus 71 infection: A new threat to global public health?","volume":"7","author":"Jane","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1473-3099(13)70342-6","article-title":"Hand, foot, and mouth disease in China, 2008\u20132012: An epidemiological study","volume":"14","author":"Xing","year":"2014","journal-title":"Lancet Infect. 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