{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:47:04Z","timestamp":1788828424666,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T00:00:00Z","timestamp":1691798400000},"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>Bacteria resistance to antibiotics is a concerning global health problem; in this context, methicillin-resistant Staphylococcus aureus (MRSA) is considered as a high priority by the World Health Organization. Furthermore, patients with a positive result for COVID-19 received early antibiotic treatment, a fact that potentially encourages the increase in antibiotic resistance. Therefore, there is an urgency to develop new drugs with molecular mechanisms different from those of the actual treatments. In this context, enzymes from the shikimate pathway, a route absent in humans, such as dehydroquinate dehydratase (DHQD), are considered good targets. In this work, a computer-aided drug design strategy, which involved exhaustive virtual screening and molecular dynamics simulations with MM-PBSA analysis, as well as an in silico ADMETox characterization, was performed to find potential noncovalent inhibitors of DHQD from MRSA (SaDHQD). After filtering the 997 million compounds from the ZINC database, 6700 compounds were submitted to an exhaustive virtual screening protocol. From these data, four molecules were selected and characterized (ZINC000005753647 (1), ZINC000001720488 (2), ZINC000082049768 (3), and ZINC000644149506 (4)). The results indicate that the four potential inhibitors interacted with residues important for substrate binding and catalysis, with an estimated binding free energy like that of the enzyme\u2019s substrate. Their ADMETox-predicted properties suggest that all of them support the structural characteristics to be considered good candidates. Therefore, the four compounds reported here are excellent option to be considered for future in vitro studies to design new SaDHQD noncovalent inhibitors and contribute to the search for new drugs against MRSA.<\/jats:p>","DOI":"10.3390\/ph16081148","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"1148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of Potential Noncovalent Inhibitors of Dehydroquinate Dehydratase from Methicillin-Resistant Staphylococcus aureus through Computational-Driven Drug Design"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-6504","authenticated-orcid":false,"given":"C\u00e9sar","family":"Mill\u00e1n-Pacheco","sequence":"first","affiliation":[{"name":"Facultad de Farmacia, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lluvia","family":"Rios-Soto","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n, Universidad Ju\u00e1rez del Estado de Durango, Av. Universidad y Fanny Anitua S\/N, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9","family":"Corral-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n, Universidad Ju\u00e1rez del Estado de Durango, Av. Universidad y Fanny Anitua S\/N, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-4045","authenticated-orcid":false,"given":"Erick","family":"Sierra-Campos","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Ju\u00e1rez del Estado de Durango Campus G\u00f3mez Palacio, Avenida Art\u00edculo 123 S\/N, Fracc. Filadelfia, G\u00f3mez Palacio 35010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Valdez-Solana","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Ju\u00e1rez del Estado de Durango Campus G\u00f3mez Palacio, Avenida Art\u00edculo 123 S\/N, Fracc. Filadelfia, G\u00f3mez Palacio 35010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-4111","authenticated-orcid":false,"given":"Alfredo","family":"T\u00e9llez-Valencia","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n, Universidad Ju\u00e1rez del Estado de Durango, Av. Universidad y Fanny Anitua S\/N, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Avitia-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n, Universidad Ju\u00e1rez del Estado de Durango, Av. Universidad y Fanny Anitua S\/N, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,12]]},"reference":[{"key":"ref_1","unstructured":"O\u2019Neill, J. (2021, December 23). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations, Government of the United Kingdom. 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