{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:27:01Z","timestamp":1791584821714,"version":"4.3.4"},"reference-count":171,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minist\u00e8re de l\u2019Enseignement sup\u00e9rieur, de la Recherche et de l\u2019Innovation, Ecole doctorale 250 grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Non-polio enteroviruses (NPEVs), namely coxsackieviruses (CV), echoviruses (E), enteroviruses (EV), and rhinoviruses (RV), are responsible for a wide variety of illnesses. Some infections can progress to life-threatening conditions in children or immunocompromised patients. To date, no treatments have been approved. Several molecules have been evaluated through clinical trials without success. To overcome these failures, the multi-target directed ligand (MTDL) strategy could be applied to tackle enterovirus infections. This work analyzes registered clinical trials involving antiviral drugs to highlight the best candidates and develops filters to apply to a selection for MTDL synthesis. We explicitly stated the methods used to answer the question: which solution can fight NPEVs effectively? We note the originality and relevance of this proposal in relation to the state of the art in the enterovirus-inhibitors field. Several combinations are possible to broaden the antiviral spectrum and potency. We discuss data related to the virus and data related to each LEAD compound identified so far. Overall, this study proposes a perspective on different strategies to overcome issues identified in clinical trials and evaluate the \u201cMTDL\u201d potential to improve the efficacy of drugs, broaden the antiviral targets, possibly reduce the adverse effects, drug design costs and limit the selection of drug-resistant virus variants.<\/jats:p>","DOI":"10.3390\/ph17091218","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T07:36:00Z","timestamp":1726472160000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["From the \u201cOne-Molecule, One-Target, One-Disease\u201d Concept towards Looking for Multi-Target Therapeutics for Treating Non-Polio Enterovirus (NPEV) Infections"],"prefix":"10.3390","volume":"17","author":[{"given":"Hugo","family":"Roux","sequence":"first","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CNRS, ICR UMR_7273, LPCR, Facult\u00e9 de Pharmacie, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4734-2249","authenticated-orcid":false,"given":"Franck","family":"Touret","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Virus \u00c9mergents (UVE: Aix-Marseille Universit\u00e9, Universit\u00e0 di Corsica, IRD 190, Inserm 1207, IRBA), 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-5862","authenticated-orcid":false,"given":"Pascal","family":"Rathelot","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CNRS, ICR UMR_7273, LPCR, Facult\u00e9 de Pharmacie, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-829X","authenticated-orcid":false,"given":"Patrice","family":"Vanelle","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CNRS, ICR UMR_7273, LPCR, Facult\u00e9 de Pharmacie, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-9173","authenticated-orcid":false,"given":"Manon","family":"Roche","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CNRS, ICR UMR_7273, LPCR, Facult\u00e9 de Pharmacie, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"ref_1","unstructured":"(2003). 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