{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T04:44:46Z","timestamp":1786164286115,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"29","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:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22077142"],"award-info":[{"award-number":["22077142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Targeted protein degradation (TPD) using proteolysis\u2010targeting chimeras (PROTACs) offers advantages over occupancy\u2010based inhibitors but faces challenges,\u00a0including ligand discovery and cellular permeability. To address these limitations, we developed\n                    <jats:bold>Re2<\/jats:bold>\n                    , a metallo\u2010PROTAC integrating a covalent rhenium(I) complex warhead targeting SARS\u2010CoV\u20102 main protease (Mpro) Cys145 with the cereblon E3 ligase ligand pomalidomide.\n                    <jats:bold>Re2<\/jats:bold>\n                    induced effective intracellular Mpro degradation at 100\u00a0nM within 72 h, which is significantly below its parent complex's enzymatic inhibition concentration. In vitro and ex vivo studies confirmed covalent Mpro binding and ubiquitin\u2010proteasome system\u2010dependent degradation. Crucially,\n                    <jats:bold>Re2<\/jats:bold>\n                    exhibited three\u2010 to fourfold higher cellular uptake and greater intracellular accumulation than its demetallated organic counterpart, demonstrating that metalation overcomes intrinsic PROTAC permeability barriers. This work establishes metallo\u2010PROTACs, exploiting the tunable coordination chemistry of metal complexes for enhanced target engagement and cellular delivery, as a potent strategy for designing high\u2010potent PROTACs.\n                  <\/jats:p>","DOI":"10.1002\/chem.202503042","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:59:32Z","timestamp":1764507572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tricarbonyl Rhenium\u2010Based PROTACs Degrade the SARS\u2010CoV\u20102 Mpro Protease"],"prefix":"10.1002","volume":"32","author":[{"given":"Liuruiqi","family":"Luo","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry Sun Yat\u2010Sen University  Guangzhou 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IGCME, School of Chemistry Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Xiong","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry Sun Yat\u2010Sen University  Guangzhou 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