{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:16Z","timestamp":1785432496863,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012352","name":"University of Milan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["315018\/2023-2"],"award-info":[{"award-number":["315018\/2023-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"award":["315018\/2023-2"],"award-info":[{"award-number":["315018\/2023-2"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>This review offers a critical and comprehensive overview of the most promising covalent inhibitors against traditional and emerging enzymatic targets of Mycobacterium tuberculosis (Mtb). Nearly three decades after the World Health Organisation\u2019s (WHO) declaration of tuberculosis (TB) as a global health emergency, Mtb continues to claim millions of lives, remaining among the leading causes of death worldwide. In recent years, several efforts have been devoted to shortening and improving treatment outcomes and to overcoming increasing drug resistance. The aim of our work is to provide a perspective on recent progress in the field of covalent inhibitors of mycobacterial enzymes, highlighting the current landscape and outlining future directions for safer and more effective strategies.<\/jats:p>","DOI":"10.3390\/ph19050707","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:47:28Z","timestamp":1777546048000},"page":"707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Covalent Inhibitors Targeting Mycobacterial Enzymes: Current Status, Challenges and Future Perspectives"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-9985","authenticated-orcid":false,"given":"Mariana Luiza","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory for Synthesis of Medicinal Molecules (LaSMMed), Department of Chemistry, State University of Londrina, Rodovia Celso Garcia Cid (PR-445), Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7491-1494","authenticated-orcid":false,"given":"Matteo","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Luigi Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0636-7589","authenticated-orcid":false,"given":"Stefania","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Luigi Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7190-380X","authenticated-orcid":false,"given":"Andrea","family":"Tresoldi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Luigi Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6511-7360","authenticated-orcid":false,"given":"Fiorella","family":"Meneghetti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Luigi Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6001-360X","authenticated-orcid":false,"given":"Marcelle de Lima Ferreira","family":"Bispo","sequence":"additional","affiliation":[{"name":"Laboratory for Synthesis of Medicinal Molecules (LaSMMed), Department of Chemistry, State University of Londrina, Rodovia Celso Garcia Cid (PR-445), Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/cmdc.201900107","article-title":"Covalent Inhibition in Drug Discovery","volume":"14","author":"Ghosh","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14693","DOI":"10.1021\/acs.jmedchem.4c01721","article-title":"Demystifying Functional Parameters for Irreversible Enzyme Inhibitors","volume":"67","author":"Heppner","year":"2024","journal-title":"J. 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