{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:10:52Z","timestamp":1790212252971,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SiciliAn MicronanOTecH Research and Innovation CEnter \u201cSAMOTHRACE\u201d","award":["PNRR-M4C2"],"award-info":[{"award-number":["PNRR-M4C2"]}]},{"name":"SiciliAn MicronanOTecH Research and Innovation CEnter \u201cSAMOTHRACE\u201d","award":["ECS_00000022"],"award-info":[{"award-number":["ECS_00000022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series\u2019 of small molecules with a significant affinity for SARS-CoV-2 MPRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The Biotarget Predictor Tool was used to filter a large in-house structural database and select a set of benzo[b]thiophene and benzo[b]furan derivatives. ADME properties were investigated, and induced fit docking studies were performed to confirm the DRUDIT prediction. Principal component analysis and docking protocol at the SARS-CoV-2 MPRO dimerization site enable the identification of compounds 1b,c,i,l and 2i,l as promising drug molecules, showing favorable dual binding site affinity on SARS-CoV-2 MPRO.<\/jats:p>","DOI":"10.3390\/ijms24098377","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T03:34:53Z","timestamp":1683516893000},"page":"8377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In Silico Design of New Dual Inhibitors of SARS-CoV-2 MPRO through Ligand- and Structure-Based Methods"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-4920","authenticated-orcid":false,"given":"Alessia","family":"Bono","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-6815","authenticated-orcid":false,"given":"Antonino","family":"Lauria","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-1943","authenticated-orcid":false,"given":"Gabriele","family":"La Monica","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8281-3511","authenticated-orcid":false,"given":"Federica","family":"Alamia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mingoia","sequence":"additional","affiliation":[{"name":"Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), Consiglio Nazionale delle Ricerche (CNR), Via Ugo La Malfa, 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-1882","authenticated-orcid":false,"given":"Annamaria","family":"Martorana","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche \u201cSTEBICEF\u201d, University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105948","DOI":"10.1016\/j.ijantimicag.2020.105948","article-title":"Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence","volume":"55","author":"Wang","year":"2020","journal-title":"Int. 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