{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:02:35Z","timestamp":1787497355337,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Botulinum toxins are neurotoxins produced by Clostridium botulinum. This toxin can be lethal for humans as a cause of botulism; however, in small doses, the same toxin is used to treat different conditions. Even if the therapeutic doses are effective and safe, the adverse reactions could be local and could unmask a subclinical impairment of neuromuscular transmissions. There are not many cases of adverse events in the literature; however, it is possible that sometimes they do not occur as they are transient and, if they do occur, there is no possibility of a cure other than to wait for the pharmacological effect to end. Inhibition of botulinum neurotoxin type A (BoNT\/A) effects is a strategy for treating botulism as it can provide an effective post-exposure remedy. In this paper, 13,592,287 compounds were screened through a pharmacophore filter, a 3D-QSAR model, and a virtual screening; then, the compounds with the best affinity were selected. Molecular dynamics simulation studies on the first four compounds predicted to be the most active were conducted to verify that the poses foreseen by the docking were stable. This approach allowed us to identify compounds with a calculated inhibitory activity in the range of 316\u2013500 nM.<\/jats:p>","DOI":"10.3390\/ijms21249470","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T23:39:36Z","timestamp":1607902776000},"page":"9470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["An Integrated Pharmacophore\/Docking\/3D-QSAR Approach to Screening a Large Library of Products in Search of Future Botulinum Neurotoxin A Inhibitors"],"prefix":"10.3390","volume":"21","author":[{"given":"Davide","family":"Gentile","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-1260","authenticated-orcid":false,"given":"Giuseppe","family":"Floresta","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-2631","authenticated-orcid":false,"given":"Vincenzo","family":"Patamia","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1256-7605","authenticated-orcid":false,"given":"Rita","family":"Chiaramonte","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Via S. Sofia 67, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-6730","authenticated-orcid":false,"given":"Giulia Letizia","family":"Mauro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology, and Stomatology, University of Palermo, Via Liborio Giuffr\u00e8 5, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-2151","authenticated-orcid":false,"given":"Antonio","family":"Rescifina","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Via S. 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