{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:20:10Z","timestamp":1777087210383,"version":"3.51.4"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["20\/FFP\u2010P\/8760"],"award-info":[{"award-number":["20\/FFP\u2010P\/8760"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    The COVID\u201019 pandemic highlighted the urgent need for effective antiviral treatments targeting SARS\u2010CoV\u20102. TMPRSS2, a serine protease essential for viral entry into host cells, represents a promising therapeutic target, and this study explores guanidino diaryl thioureas as potential TMPRSS2 inhibitors. Initial screening identified a \u201chit\u2010compound\u201d (\n                    <jats:bold>1<\/jats:bold>\n                    ) with reversible inhibitory activity against TMPRSS2. Computational studies, including docking and molecular dynamics simulations, were conducted to optimize derivatives of compound\n                    <jats:bold>1<\/jats:bold>\n                    . Twenty\u2010five derivatives were synthesized, and their pharmacokinetic properties and cytotoxicity assessments indicated favorable drug\u2010likeness and minimal toxicity. However, biochemical studies revealed that none of the derivatives improved TMPRSS2 inhibitory activity compared to the original \u201chit\u2010compound\u201d. The findings suggest that reversible inhibitors may be suboptimal for TMPRSS2 targeting, as camostat and nafamostat exert their effects through irreversible covalent binding. Future efforts should focus on developing irreversible TMPRSS2 inhibitors to enhance antiviral efficacy against SARS\u2010CoV\u20102.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501000","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:33:31Z","timestamp":1764542011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Searching for Novel Antiviral Agents as COVID19 Treatments: Guanidino Diaryl Thioureas"],"prefix":"10.1002","volume":"21","author":[{"given":"Marco","family":"Minneci","sequence":"first","affiliation":[{"name":"School of Chemistry Trinity College Dublin The University of Dublin TBSI  Dublin D02R590 Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Farka\u0161","sequence":"additional","affiliation":[{"name":"School of Chemistry Trinity College Dublin The University of Dublin TBSI  Dublin D02R590 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