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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>1,2-Benzothiazine derivatives have attracted attention as structurally versatile scaffolds for antiviral drug discovery. Their sulfur-containing heterocyclic core supports diverse substitution patterns, allowing modulation of physicochemical properties and biological activity through medicinal chemistry optimization. This review summarizes published studies on 1,2-benzothiazine-based derivatives as potential inhibitors of human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with particular emphasis on structure\u2013activity relationships (SAR). Comprehensive SAR analyses indicate that substitutions at the N-1 and C-3 positions play a pivotal role in modulating antiviral potency and selectivity. Among the reported compounds, the most selective anti-HIV agent was a pyrazole-substituted 1,2-benzothiazine (9h) bearing a 2-amino-4-methylthiazolehydrazidoacetyl moiety, which exhibited an EC50 value of 3.8 \u03bcM against HIV-1 in primary human peripheral blood mononuclear cells. For HCV, the most promising derivative was a pyrazolebenzothiazine (5b) containing a 4-chloro substituent in the N-1 phenyl ring and a p-methanesulfonamidophenyl group at the C-3 position, demonstrating an IC50 value of 7.9 \u03bcM in the NS5B polymerase assay. Despite showing antiviral activity against both HIV and HCV, all tested compounds, including the most active derivatives, were considerably less potent than the corresponding reference drugs. Further optimization is therefore needed to improve their antiviral potency.<\/jats:p>","DOI":"10.3390\/ijms27177800","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["1,2-Benzothiazine Derivatives as Anti-HIV and Anti-HCV Agents: Structure\u2013Activity Relationships and Research Perspectives"],"prefix":"10.3390","volume":"27","author":[{"given":"Izabela","family":"Topolska","sequence":"first","affiliation":[{"name":"Student Science Club of Medicinal Chemistry, Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-5760","authenticated-orcid":false,"given":"Berenika M.","family":"Szcz\u0119\u015bniak-Si\u0119ga","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lozach, P.-Y. 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