{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:07:47Z","timestamp":1789625267768,"version":"build-2803163510"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOST | National Key Research and Development Program of China","award":["2021YFD1801104"],"award-info":[{"award-number":["2021YFD1801104"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,5,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Coronavirus (CoV) 3C-like protease (3CL\n              <jats:sup>pro<\/jats:sup>\n              ) is essential for viral replication and is involved in immune escape by proteolyzing host proteins. Deep profiling the 3CL\n              <jats:sup>pro<\/jats:sup>\n              substrates in the host proteome extends our understanding of viral pathogenesis and facilitates antiviral drug discovery. Here, 3CL\n              <jats:sup>pro<\/jats:sup>\n              from porcine epidemic diarrhea virus (PEDV), an enteropathogenic CoV, was used as a model which to identify the potential 3CL\n              <jats:sup>pro<\/jats:sup>\n              cleavage motifs in all porcine proteins. We characterized the selectivity of PEDV 3CL\n              <jats:sup>pro<\/jats:sup>\n              at sites P5\u2013P4\u2032. We then compiled the 3CL\n              <jats:sup>pro<\/jats:sup>\n              substrate preferences into a position-specific scoring matrix and developed a 3CL\n              <jats:sup>pro<\/jats:sup>\n              profiling strategy to delineate the protein substrate landscape of CoV 3CL\n              <jats:sup>pro<\/jats:sup>\n              . We identified 1,398 potential targets in the porcine proteome containing at least one putative cleavage site and experimentally validated the reliability of the substrate degradome. The PEDV 3CL\n              <jats:sup>pro<\/jats:sup>\n              -targeted pathways are involved in mRNA processing, translation, and key effectors of autophagy and the immune system. We also demonstrated that PEDV 3CL\n              <jats:sup>pro<\/jats:sup>\n              suppresses the type 1 interferon (IFN-I) cascade\n              <jats:italic>via<\/jats:italic>\n              the proteolysis of multiple signaling adaptors in the retinoic acid-inducible gene I (RIG-I) signaling pathway. Our composite method is reproducible and accurate, with an unprecedented depth of coverage for substrate motifs. The 3CL\n              <jats:sup>pro<\/jats:sup>\n              substrate degradome establishes a comprehensive substrate atlas that will accelerate the investigation of CoV pathogenicity and the development of anti-CoV drugs.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Coronaviruses (CoVs) are major pathogens that infect humans and animals. The 3C-like protease (3CL\n                <jats:sup>pro<\/jats:sup>\n                ) encoded by CoV not only cleaves the CoV polyproteins but also degrades host proteins and is considered an attractive target for the development of anti-CoV drugs. However, the comprehensive characterization of an atlas of CoV 3CL\n                <jats:sup>pro<\/jats:sup>\n                substrates is a long-standing challenge. Using porcine epidemic diarrhea virus (PEDV) 3CL\n                <jats:sup>pro<\/jats:sup>\n                as a model, we developed a method that accurately predicts the substrates of 3CL\n                <jats:sup>pro<\/jats:sup>\n                and comprehensively maps the substrate degradome of PEDV 3CL\n                <jats:sup>pro<\/jats:sup>\n                . Interestingly, we found that 3CL\n                <jats:sup>pro<\/jats:sup>\n                may simultaneously degrade multiple molecules responsible for a specific function. For instance, it cleaves at least four adaptors in the RIG-I signaling pathway to suppress type 1 interferon production. These findings highlight the complexity of the 3CL\n                <jats:sup>pro<\/jats:sup>\n                substrate degradome and provide new insights to facilitate the development of anti-CoV drugs.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00253-24","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T13:01:17Z","timestamp":1712667677000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Deep profiling of potential substrate atlas of porcine epidemic diarrhea virus 3C-like protease"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-3682","authenticated-orcid":false,"given":"Junwei","family":"Zhou","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Sun","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Qiu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Yang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Guo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-9188","authenticated-orcid":true,"given":"Shaobo","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-6409","authenticated-orcid":true,"given":"Liurong","family":"Fang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"},{"name":"The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig 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CCP4 Newsl Protein Crystallogr 40:82\u201392.","journal-title":"CCP4 Newsl Protein Crystallogr"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00253-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00253-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T13:04:08Z","timestamp":1715691848000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00253-24"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,14]]}},"alternative-id":["10.1128\/jvi.00253-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00253-24","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]},"assertion":[{"value":"2024-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00253-24"}}