{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:26:40Z","timestamp":1787909200535,"version":"build-2784847793"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["32473022"],"award-info":[{"award-number":["32473022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Major Science and Technology Projects in GANSU Province","award":["23ZDNA007"],"award-info":[{"award-number":["23ZDNA007"]}]},{"name":"Innovation Program of Chinese Academy of Agricultural Sciences","award":["CAAS-ASTIP202434IUA07"],"award-info":[{"award-number":["CAAS-ASTIP202434IUA07"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,11,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Swine Alpha-coronaviruses are one of the most destructive pathogens affecting the swine industries across the world. Swine Alpha-coronaviruses include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus, porcine respiratory coronavirus, and swine acute diarrhea syndrome coronavirus (SADS-CoV). Thus far, swine Alpha-coronaviruses treatment options are very limited. Therefore, the identification of safe and effective treatment of swine Alpha-coronaviruses is urgently needed. In the current study, we screened a library of 240 FDA-approved compounds for antiviral activity against TGEV. Among screening, the 3CL protease inhibitor PF-00835231 was shown to dramatically inhibit TGEV replication\n              <jats:italic>in vitro<\/jats:italic>\n              systems. Mechanistically, PF-00835231 inhibits nonstructural protein 5 (Nsp5) protease activity targeting the cleavage at Nsp5\u2013Nsp6 of TGEV. Additionally, PF-00835231 exhibited the potent broad-spectrum swine Alpha-coronaviruses antiviral activity. Treatment of PF-00835231 in mice not only blocks SADS-CoV deadly infection but also dramatically reduces viral copies. Taken together, our study provides evidence that PF-00835231 may control of the current swine Alpha-coronaviruses and emerging swine Alpha-coronaviruses in the future.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>The COVID-19 pandemic has induced tremendous efforts to develop therapeutic strategies that target Beta-coronavirus including SARS-CoV-2. 3CL protease of Beta-coronavirus has been as a drug target for developing antiviral drugs. However, 3CL protease is not conserved in Alpha-coronavirus and Beta-coronavirus with only 44% amino acid similarity. Therefore, an inhibitor that prevents Alpha-coronaviruses infection is urgently needed. Swine Alpha-coronaviruses are one of the most destructive pathogens affecting the swine industries across the world. Swine herds with coronavirus diarrhea showed a high rate of co-infection between different Alpha-coronavirus. Our study, for the first time, showed that PF-00835231 inhibits swine Alpha-coronavirus infection. At the mechanistic level, we experimentally identified that PF-00835231 inhibits nonstructural protein 5 (Nsp5) protease activity targeting the cleavage at Nsp5\u2013Nsp6 of Alpha-coronaviruses.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01303-24","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T13:00:47Z","timestamp":1730379647000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["PF-00835231 broadly inhibits swine Alpha-coronavirus, including emerging SADS-CoV"],"prefix":"10.1128","volume":"98","author":[{"given":"Lei","family":"Shi","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maowen","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6850-1379","authenticated-orcid":false,"given":"Haixue","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-2410","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China"},{"name":"Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China"},{"name":"Chengdu National Agricultural Science and Technology Center, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-021-00364-0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2021.651999"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11259-021-09808-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2016.05.030"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16876-4"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2207.160179"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.12579"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2201.150544"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.13666"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.8b00435"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13091866"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.628526"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-020-00865-y"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14061231"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2021.10.026"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13091825"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.104651"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00221-18"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01819-20"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20200029"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14907"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00065-22"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00190-23"},{"key":"e_1_3_4_25_2","first-page":"445","article-title":"Current aspects in the etiology of viral diarrheas of swine: occurrence of infections with the epizootic viral diarrhea (EVD) virus","volume":"93","author":"Hess RG","year":"1980","unstructured":"Hess RG, Bollwahn W, Pospischil A, Heinritzi K, Bachmann PA. 1980. Current aspects in the etiology of viral diarrheas of swine: occurrence of infections with the epizootic viral diarrhea (EVD) virus. Berl Munch Tierarztl Wochenschr 93:445\u2013449.","journal-title":"Berl Munch Tierarztl Wochenschr"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1803.120002"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01448-19"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12020135"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3405"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11010059"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.1.177-185.1999"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1870414"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085658"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01577-x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3475"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26239-2"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01063"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21953"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01256-17"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01303-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01303-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T14:02:22Z","timestamp":1732024942000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01303-24"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,19]]}},"alternative-id":["10.1128\/jvi.01303-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01303-24","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]},"assertion":[{"value":"2024-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01303-24"}}