{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T08:07:26Z","timestamp":1783843646480,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    A new series of substituted 1,3,4\u2010thiadiazole\u20131,3,5\u2010triazine hybrids was rationally designed, synthesized, and evaluated for their antiviral and antibacterial potential. The target di\u2010substituted (\n                    <jats:bold>9a\u2013e<\/jats:bold>\n                    ) and tri\u2010substituted (\n                    <jats:bold>11a\u2013e<\/jats:bold>\n                    ) derivatives were obtained via a stepwise nucleophilic substitution strategy from cyanuric chloride and characterized by spectroscopic techniques. Molecular docking studies against human immunodeficiency virus\u20101 reverse transcriptase (HIV\u20101 RT) revealed that\n                    <jats:italic>para<\/jats:italic>\n                    \u2010substituted analogs displayed superior binding within the non\u2010nucleoside reverse transcriptase inhibitor pocket through key hydrogen bonding,\n                    <jats:italic>\u03c0\u2013\u03c0<\/jats:italic>\n                    stacking, and electrostatic interactions. In vitro evaluation identified compounds\n                    <jats:bold>11a<\/jats:bold>\n                    as the most active candidate. Compound\n                    <jats:bold>11a<\/jats:bold>\n                    exhibited 83.93% inhibition of RT activity at 1 \u03bcM, an EC\n                    <jats:sub>50<\/jats:sub>\n                    of 72.7\u2009nM, and effective suppression of HIV\u20101 replication in CEM\u2013GFP T cells (85.19% p24 inhibition) with a favorable therapeutic index (TI\u2009=\u2009471). Both compounds also demonstrated inhibition of SARS\u2010CoV\u20102\u2010induced cytopathic effects in Vero E6 cells at noncytotoxic concentrations. In addition, several derivatives showed moderate to good antibacterial activity against tested bacterial strains, with SAR analysis highlighting the importance of substituent electronics and positional effects on bioactivity. Overall, this study establishes substituted 1,3,4\u2010thiadiazole\u20131,3,5\u2010triazine hybrids as promising multifunctional scaffolds for antiviral and antibacterial drug development.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501109","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:41:27Z","timestamp":1774928487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Discovery of Substituted 1,3,4\u2010Thiadiazole\u20131,3,5\u2010Triazine Hybrids as Human Immunodeficiency Virus\u20101 Non\u2010Nucleoside Reverse Transcriptase Inhibitors with Anti\u2010SARS\u2010CoV\u20102 and Antibacterial Activities"],"prefix":"10.1002","volume":"21","author":[{"given":"Saumya","family":"Singh","sequence":"first","affiliation":[{"name":"Drug Design &amp; Discovery Laboratory Department of Pharmaceutical Sciences, Shalom Institute of Health and Allied Sciences Sam Higginbottom University of Agriculture, Technology &amp; Sciences  Prayagraj Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar Saurabh","family":"Srivastava","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science SP Pune University Campus  Pune Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh Kumar","family":"Kumawat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dr. Harisingh Gour University  Sagar Madhya Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Raj","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Corona","sequence":"additional","affiliation":[{"name":"Laboratorio di Virologia Molecolare Dipartimento di Scienze della Vita e Dell\u2019Ambiente Universit\u00e0 degli Studi di Cagliari Cittadella Universitaria di Monserrato  Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Laboratorio di Virologia Molecolare Dipartimento di Scienze della Vita e Dell\u2019Ambiente Universit\u00e0 degli Studi di Cagliari Cittadella Universitaria di Monserrato  Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debashis","family":"Mitra","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science SP Pune University Campus  Pune Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0865-0502","authenticated-orcid":false,"given":"Udaya Pratap","family":"Singh","sequence":"additional","affiliation":[{"name":"Drug Design &amp; Discovery Laboratory Department of Pharmaceutical Sciences, Shalom Institute of Health and Allied Sciences Sam Higginbottom University of Agriculture, Technology &amp; Sciences  Prayagraj Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000588"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1068664"},{"key":"e_1_2_11_4_1","volume-title":"HIV\u20101 Associated Opportunistic Infections","author":"Justiz Vaillant A. 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