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In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)<jats:italic>trans<\/jats:italic>-epoxysuccinyl-<jats:sc>l<\/jats:sc>-leucylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.<\/jats:p>","DOI":"10.1128\/jvi.00094-12","type":"journal-article","created":{"date-parts":[[2012,4,12]],"date-time":"2012-04-12T05:16:50Z","timestamp":1334207810000},"page":"6537-6545","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":468,"title":["Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry"],"prefix":"10.1128","volume":"86","author":[{"given":"Miyuki","family":"Kawase","sequence":"first","affiliation":[{"name":"Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, Gakuen Musashi-Murayama, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Shirato","sequence":"additional","affiliation":[{"name":"Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, Gakuen Musashi-Murayama, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"van der Hoek","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Amsterdam, Faculty of Earth and Life Sciences, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiro","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Kyonan-cho, Musashino, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutoku","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, Gakuen Musashi-Murayama, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809524106"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.103275"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00239-10"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05300-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.657"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00415-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.03.029"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01118-06"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00140-10"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01294-10"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02205-08"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.05.003"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1440"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80955-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02232-10"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508381200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007870"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01933-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01542-10"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503203102"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00959-09"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.046"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02605-09"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4845"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00464-11"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00676-08"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02062-10"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.02.020"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505577102"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306446101"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1440-1746.2007.05206.x","article-title":"Pancreatic stellate cells: new target in the treatment of chronic pancreatitis","volume":"23","author":"Talukdar R","year":"2008","unstructured":"TalukdarR TandonRK. 2008. 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