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By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein\u2019s crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport\u00ae. The ADME\/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of \u22128.645 kcal\u00b7mol\u22121, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC50 values (ranging from 0.459 to 2.371 \u00b5M) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.<\/jats:p>","DOI":"10.3390\/ijms24108814","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"8814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Design and Identification of Inhibitors for the Spike-ACE2 Target of SARS-CoV-2"],"prefix":"10.3390","volume":"24","author":[{"given":"Ruan S.","family":"Bastos","sequence":"first","affiliation":[{"name":"Graduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Par\u00e1, Belem 66075-110, PA, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macapa 68903-419, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00facio R. de","family":"Lima","sequence":"additional","affiliation":[{"name":"Graduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Par\u00e1, Belem 66075-110, PA, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macapa 68903-419, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moys\u00e9s F. 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