{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:43:07Z","timestamp":1776292987286,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a serious global public health threat. The evolving strains of SARS-CoV-2 have reduced the effectiveness of vaccines. Therefore, antiviral drugs against SARS-CoV-2 are urgently needed. The main protease (Mpro) of SARS-CoV-2 is an extremely potent target due to its pivotal role in virus replication and low susceptibility to mutation. In the present study, a quantitative structure\u2013activity relationship (QSAR) study was performed to design new molecules that might have higher inhibitory activity against SARS-CoV-2 Mpro. In this context, a set of 55 dihydrophenanthrene derivatives was used to build two 2D-QSAR models using the Monte Carlo optimization method and the Genetic Algorithm Multi-Linear Regression (GA-MLR) method. From the CORAL QSAR model outputs, the promoters responsible for the increase\/decrease in inhibitory activity were extracted and interpreted. The promoters responsible for an increase in activity were added to the lead compound to design new molecules. The GA-MLR QSAR model was used to ensure the inhibitory activity of the designed molecules. For further validation, the designed molecules were subjected to molecular docking analysis and molecular dynamics simulations along with an absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. The results of this study suggest that the newly designed molecules have the potential to be developed as effective drugs against SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/ph16040608","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:18:13Z","timestamp":1681795093000},"page":"608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Design of Potent Inhibitors Targeting the Main Protease of SARS-CoV-2 Using QSAR Modeling, Molecular Docking, and Molecular Dynamics Simulations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-0537","authenticated-orcid":false,"given":"Mehdi","family":"Oubahmane","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, BP 2390, Marrakech 40000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-5131","authenticated-orcid":false,"given":"Ismail","family":"Hdoufane","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, BP 2390, Marrakech 40000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christelle","family":"Delaite","sequence":"additional","affiliation":[{"name":"Laboratoire de Photochimie et d\u2019Ing\u00e9nierie Macromol\u00e9culaires (LPIM), Ecole Nationale Sup\u00e9rieure de Chimie de Mulhouse, Universit\u00e9 de Haute-Alsace, 68100 Mulhouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-394X","authenticated-orcid":false,"given":"Adlane","family":"Sayede","sequence":"additional","affiliation":[{"name":"University Artois, CNRS, Centrale Lille, University Lille, UMR 8181, Unit\u00e9 de Catalyse et Chimie du Solide (UCCS), F-62300 Lens, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Driss","family":"Cherqaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, BP 2390, Marrakech 40000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-2161","authenticated-orcid":false,"given":"Achraf","family":"El Allali","sequence":"additional","affiliation":[{"name":"African Genome Center, Mohammed VI Polytechnic University, Ben Guerir 43150, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.2174\/1568026622666220726122339","article-title":"Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview","volume":"22","author":"Oubahmane","year":"2022","journal-title":"Curr. 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