{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:36:21Z","timestamp":1789522581952,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2311-B-241-001"],"award-info":[{"award-number":["109-2311-B-241-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["CH-DMR-110-006"],"award-info":[{"award-number":["CH-DMR-110-006"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["DMR-107-022"],"award-info":[{"award-number":["DMR-107-022"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Medical University Hsinchu Hospital","award":["109-2311-B-241-001"],"award-info":[{"award-number":["109-2311-B-241-001"]}]},{"name":"China Medical University Hsinchu Hospital","award":["CH-DMR-110-006"],"award-info":[{"award-number":["CH-DMR-110-006"]}]},{"name":"China Medical University Hsinchu Hospital","award":["DMR-107-022"],"award-info":[{"award-number":["DMR-107-022"]}]},{"name":"China Medical University Hospital","award":["109-2311-B-241-001"],"award-info":[{"award-number":["109-2311-B-241-001"]}]},{"name":"China Medical University Hospital","award":["CH-DMR-110-006"],"award-info":[{"award-number":["CH-DMR-110-006"]}]},{"name":"China Medical University Hospital","award":["DMR-107-022"],"award-info":[{"award-number":["DMR-107-022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 \u00c5. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46\u201349 in animal coronaviral Mpros has been replaced by a stable \u03b1-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.<\/jats:p>","DOI":"10.3390\/ijms23105669","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:59:37Z","timestamp":1652875177000},"page":"5669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Structural Comparison of SARS-CoV-2 Main Protease and Animal Coronaviral Main Protease Reveals Species-Specific Ligand Binding and Dimerization Mechanism"],"prefix":"10.3390","volume":"23","author":[{"given":"Chien-Yi","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan"},{"name":"Division of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan"},{"name":"Physical Examination Center, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan"},{"name":"Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"AI Innovation Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-9731","authenticated-orcid":false,"given":"Yu-Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9580-7418","authenticated-orcid":false,"given":"Yu-Chuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Translational Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fang","family":"Chiu","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7653-8147","authenticated-orcid":false,"given":"Shu-Jung","family":"Lai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"},{"name":"Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Applied Cosmetology, Hungkuang University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-8716","authenticated-orcid":false,"given":"Wei-Chien","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"},{"name":"Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Drug Development Center, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Tien","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-0446","authenticated-orcid":false,"given":"Yeh","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, China Medical University, Taichung 404, Taiwan"},{"name":"Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan"},{"name":"Drug Development Center, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wong, A.C.P., Lau, S.K.P., and Woo, P.C.Y. 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