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However, the development of inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) PL\n                    <jats:sup>pro<\/jats:sup>\n                    is challenging owing to the restricted S1\/S2 sites in the substrate binding pocket. Here we report the discovery of two activators of SARS\u2010CoV\u20102 PL\n                    <jats:sup>pro<\/jats:sup>\n                    and the identification of the unique residue, cysteine 270 (C270), as an allosteric and covalent regulatory site for the activators. This site is also specifically modified by glutathione, resulting in protease activation. Furthermore, a compound was found to allosterically inhibit the protease activity by covalent binding to C270. Together, these results elucidate an unrevealed molecular mechanism for allosteric modulation of SARS\u2010CoV\u20102 PL\n                    <jats:sup>pro<\/jats:sup>\n                    and provid a novel site for allosteric inhibitors design.\n                  <\/jats:p>","DOI":"10.1002\/anie.202212378","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T11:04:46Z","timestamp":1667041486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of Cysteine 270 as a Novel Site for Allosteric Modulators of SARS\u2010CoV\u20102 Papain\u2010Like Protease**"],"prefix":"10.1002","volume":"61","author":[{"given":"Hangchen","family":"Hu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou 310024 China"},{"name":"CAS Key Laboratory of Receptor 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