{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:00:04Z","timestamp":1790258404401,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1303700"],"award-info":[{"award-number":["2022YFA1303700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21977007"],"award-info":[{"award-number":["21977007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2321001"],"award-info":[{"award-number":["T2321001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["2021\u2010I2M\u20105\u2010014"],"award-info":[{"award-number":["2021\u2010I2M\u20105\u2010014"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The SARS\u2010CoV\u20102 main protease (3CLpro) is an essential enzyme for viral replication and a major target for antiviral drug development. While its catalytic activity is known to require dimer formation, the mechanism by which it cleaves itself from the monomeric viral polyprotein remains to be further studied. In this study, we engineered several D\u2010peptides based on a de novo designed D\u2010peptide inhibitor. These peptides bind to the 3CLpro monomer and unexpectedly activate its catalytic function. By enhancing the turnover number, the peptides significantly boost the catalytic efficiency of 3CLpro. Among them, LY11 stands out with high binding affinity (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>D<\/jats:sub>\n                    \u2009=\u2009117\u2009nM) and strong potency of enzymatic activation (EC\n                    <jats:sub>200<\/jats:sub>\n                    \u2009&lt;\u20091\u2009\u03bcM). Through biophysical and computational approaches, we show that LY11 binds in 1:1 stoichiometry, stabilizing the monomeric state while allosterically remodeling the inter\u2010domain linker of 3CLpro to expand the substrate binding pocket and switch on the protease. These findings suggest new insights into the maturation and catalytic mechanism of 3CLpro. The LY11\u2010regulated 3CL protease may serve as a versatile molecular tool for synthetic biology applications.\n                  <\/jats:p>","DOI":"10.1002\/pro.70788","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:44:45Z","timestamp":1789479885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of D\u2010peptides that allosterically enhance\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102\n                    <scp>3CLpro<\/scp>\n                    activity by stabilizing its monomeric state"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4088-4229","authenticated-orcid":false,"given":"Laiyi","family":"Feng","sequence":"first","affiliation":[{"name":"Center for Life Sciences at BNLMS, College of Chemistry and Molecular Engineering Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2384-6928","authenticated-orcid":false,"given":"Xinliao","family":"Ling","sequence":"additional","affiliation":[{"name":"Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Bian","sequence":"additional","affiliation":[{"name":"Chengdu Academy for Advanced Interdisciplinary Biotechnologies Peking University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8990-0878","authenticated-orcid":false,"given":"Changsheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Life Sciences at BNLMS, College of Chemistry and Molecular Engineering Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8343-7587","authenticated-orcid":false,"given":"Luhua","family":"Lai","sequence":"additional","affiliation":[{"name":"Center for Life Sciences at BNLMS, College of Chemistry and Molecular Engineering Peking University  Beijing China"},{"name":"Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies Peking University  Beijing China"},{"name":"Chengdu Academy for Advanced Interdisciplinary Biotechnologies Peking University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102790","article-title":"pH profiles of 3\u2010chymotrypsin\u2010like protease (3CLpro) from SARS\u2010CoV\u20102 elucidate its catalytic mechanism and a histidine residue critical for activity","volume":"299","author":"Adem K","year":"2023","journal-title":"J Biol Chem"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20231395","article-title":"3\u2010chymotrypsin\u2010like protease in SARS\u2010CoV\u20102","volume":"44","author":"Adem K","year":"2024","journal-title":"Biosci Rep"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.2147\/DDDT.S370574","article-title":"Allosteric binding sites of the SARS\u2010CoV\u20102 main protease: potential targets for broad\u2010spectrum anti\u2010coronavirus agents","volume":"16","author":"Alzyoud L","year":"2022","journal-title":"Drug des Devel 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