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The ongoing emergency of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed severe threats to the global economy and public health, which has generated great concerns about zoonotic viruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus, was responsible for mass piglet deaths, resulting in unprecedented economic losses, and no approved drugs or vaccines are currently available for SADS-CoV infection. Given its potential ability to cause cross-species infection, it is essential to develop specific antiviral drugs and vaccines against SADS-CoV. Drug screening was performed on a total of 3523 compound-containing drug libraries as a strategy of existing medications repurposing. We identified five compounds (gemcitabine, mycophenolate mofetil, mycophenolic acid, methylene blue and cepharanthine) exhibiting inhibitory effects against SADS-CoV in a dose-dependent manner. Cepharanthine and methylene blue were confirmed to block viral entry, and gemcitabine, mycophenolate mofetil, mycophenolic acid and methylene blue could inhibit viral replication after SADS-CoV entry. This is the first report on SADS-CoV drug screening, and we found five compounds from drug libraries to be potential anti-SADS-CoV drugs, supporting the development of antiviral drugs for a possible outbreak of SADS-CoV in the future.<\/jats:p>","DOI":"10.3390\/ijms231911250","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus"],"prefix":"10.3390","volume":"23","author":[{"given":"Yangzhen","family":"Chen","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1696-9540","authenticated-orcid":false,"given":"Yecheng","family":"You","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhou","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"An","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Song","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-8045","authenticated-orcid":false,"given":"Yigang","family":"Tong","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5007-2158","authenticated-orcid":false,"given":"Huahao","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1016\/S0140-6736(21)02758-6","article-title":"Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic","volume":"398","author":"Karim","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.3201\/eid2309.170915","article-title":"A New Bat-HKU2-like Coronavirus in Swine, China, 2017","volume":"23","author":"Gong","year":"2017","journal-title":"Emerg. 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