{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:36:04Z","timestamp":1786725364085,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"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":["ChemBioChem"],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    The COVID\u201019 pandemic caused by SARS\u2010CoV\u20102 created a global health crisis, and the virus still circulates, mutates, and causes illness and death. Vaccination remains the primary defense, but effectiveness can be reduced in immunocompromised individuals and against new variants, and clinically approved antivirals are limited by side effects, drug interactions, and resistance. Herein, we propose a novel application of tanespimycin (17AAG), the chaperone heat shock protein (HSP)90 inhibitor, as an antiviral against the SARS\u2010CoV\u20102 main protease (M\n                    <jats:sup>pro<\/jats:sup>\n                    ). M\n                    <jats:sup>pro<\/jats:sup>\n                    , due to its indispensable role in viral replication and absence of expression in the host, represents a key target for drug development. Through biochemical and cell\u2010based assays, structural analysis, and resistance\u2010mutant testing, we present data showing that 17AAG covalently binds to the active\u2010site cysteine of M\n                    <jats:sup>pro<\/jats:sup>\n                    , disrupts its secondary structure, and protects cells from M\n                    <jats:sup>pro<\/jats:sup>\n                    \u2010induced toxicity more effectively than nirmatrelvir. We further showed that 17AAG retains its covalent binding and structure\u2010disrupting activity against the nirmatrelvir\u2010resistance M165I variant. Additionally, since HSP90 is important for viral protein stability, virion assembly, and modulation of host immune response, 17AAG is a promising, versatile drug candidate that could accelerate antiviral development for COVID\u201019.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70493","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:15:30Z","timestamp":1786720530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heat Shock Protein Inhibitor Tanespimycin (17AAG) Suppresses SARS\u2010CoV\u20102 Main Protease Activity and Is More Potent Than Clinically Approved Antiviral Nirmatrelvir"],"prefix":"10.1002","volume":"27","author":[{"given":"Gargi","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Life Science Shiv Nadar University  Greater Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7406-0524","authenticated-orcid":false,"given":"Shayantani","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Life Science Shiv Nadar University  Greater Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-3918","authenticated-orcid":false,"given":"Anshuman","family":"Chandra","sequence":"additional","affiliation":[{"name":"School of Physical Sciences JNU  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1397-8684","authenticated-orcid":false,"given":"Goutam","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Independent Researcher  Greater Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1609-8722","authenticated-orcid":false,"given":"Anindita","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"Department of Life Science Shiv Nadar University  Greater Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"24","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.1111\/j.1742-4658.2006.05560.x","article-title":"Ixocarpalactone a Isolated From the Mexican Tomatillo Shows Potent Antiproliferative and Apoptotic Activity in Colon Cancer Cells","volume":"273","author":"Choi J. 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