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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibito

Hoffman et al., Cell, doi:10.1016/j.cell.2020.02.052
Mar 2020  
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In Vitro study showing that SARS-CoV-2 uses ACE2 for entry and TMPRSS2 for S protein priming, and that TMPRSS2 inhibitor camostat blocked entry and may be an effective treaetment.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants1,2.
4 preclinical studies support the efficacy of bromhexine for COVID-19:
Hoffman et al., 5 Mar 2020, peer-reviewed, 13 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperBromhexineAll
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann, Hannah Kleine-Weber, , ..., Simon Schroeder, Nadine Krüger, Tanja Herrler, Sandra Erichsen, Tobias S Schiergens, Georg Herrler, Nai-Huei Wu, Andreas Nitsche, Marcel A Müller, Christian Drosten, Stefan Pöhlmann
Cell, doi:10.1016/j.cell.2020.02.052
Highlights d SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry d The spike protein of SARS-CoV-2 is primed by TMPRSS2 d Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2
DECLARATION OF INTERESTS The authors declare no competing interests. 4 (A and B) Importance of endosomal low pH (A) and activity of CatB/L or TMPRSS2 (B) for host cell entry of SARS-CoV-2 was evaluated by adding inhibitors to target cells prior to transduction. Ammonium chloride (A) blocks endosomal acidification while E-64d and camostat mesylate (B) block the activity of CatB/L and TMPRSS2, respectively. Entry into cells not treated with inhibitor was set as 100%. (C) Absence of cytotoxic effects of camostat mesylate. Calu-3 cells were treated with camostat mesylate identically as for infection experiments and cell viability was measured using a commercially available assay (CellTiter-Glo, Promega).
References
Berger Rentsch, Zimmer, A vesicular stomatitis virus replicon-based bioassay for the rapid and sensitive determination of multi-species type I interferon, PLoS ONE
Bertram, Glowacka, Blazejewska, Soilleux, Allen et al., TMPRSS2 and TMPRSS4 facilitate trypsin-independent spread of influenza virus in Caco-2 cells, J. Virol
Bertram, Heurich, Lavender, Gierer, Danisch et al., Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts, J. Virol
Brinkmann, Hoffmann, Lu ¨bke, Nehlmeier, Kra ¨mer-Ku ¨hl et al., The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells, PLoS ONE
Buchholz, Mu ¨ller, Nitsche, Sanewski, Wevering et al., Contact investigation of a case of human novel coronavirus infection treated in a German hospital, Euro Surveill
Chan, Yuan, Kok, To, Chu et al., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster, Lancet
Corman, Landt, Kaiser, Molenkamp, Meijer et al., Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Nat. Rev. Microbiol, doi:10.2807/1560-7917.ES.2020.25.3.2000045
Corman, Lienau, Witzenrath, Coronaviruses as the cause of respiratory infections
Ding, He, Zhang, Huang, Che et al., Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways, J. Pathol
Fehr, Channappanavar, Perlman, Middle East Respiratory Syndrome: Emergence of a Pathogenic Human Coronavirus, Annu. Rev. Med
Ge, Li, Yang, Chmura, Zhu et al., Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor, Nature
Gierer, Bertram, Kaup, Wrensch, Heurich et al., The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies, J. Virol
Glowacka, Bertram, Mu ¨ller, Allen, Soilleux et al., Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response, J. Virol
Gu, Gong, Zhang, Zheng, Gao et al., Multiple organ infection and the pathogenesis of SARS, J. Exp. Med
Guan, Zheng, He, Liu, Zhuang et al., Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China, Science
Haga, Yamamoto, Nakai-Murakami, Osawa, Tokunaga et al., Modulation of TNFalpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry, Proc. Natl. Acad. Sci
Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, J. Pathol
He, Li, Heck, Lustigman, Jiang, Antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design, J. Virol
Hoffmann, Mu ¨ller, Drexler, Glende, Erdt et al., Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor, Biochem. Biophys. Res. Commun
Hofmann, Hattermann, Marzi, Gramberg, Geier et al., S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients, J. Virol
Hofmann, Pyrc, Van Der Hoek, Geier, Berkhout et al., Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry, Proc. Natl. Acad. Sci
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan
Imai, Kuba, Rao, Huan, Guo et al., Angiotensin-converting enzyme 2 protects from severe acute lung failure, Nature
Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection, J. Virol, doi:10.1128/JVI.01815-18
Kawase, Shirato, Van Der Hoek, Taguchi, Matsuyama, Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry, J. Virol
Kim, Heinlein, Hackman, Nelson, Kleine-Weber et al., Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization, Mol. Cell. Biol, doi:10.1128/JVI.01381-18
Kuba, Imai, Rao, Gao, Guo et al., A crucial role of angiotensin converting, Cell
Kumar, Stecher, Li, Knyaz, Tamura, MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms, Mol Biol Evol
Lau, Woo, Li, Huang, Tsoi et al., Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats
Li, Hulswit, Widjaja, Raj, Mcbride et al., Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein, Proc. Natl. Acad. Sci
Li, Li, Farzan, Harrison, Structure of SARS coronavirus spike receptor-binding domain complexed with receptor, Science
Li, Moore, Vasilieva, Sui, Wong et al., Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus, Nature
Li, Zhang, Sui, Kuhn, Moore et al., Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2, EMBO J
Lin, Zhang, Su, Xu, Wang et al., Safety and immunogenicity from a phase I trial of inactivated severe acute respiratory syndrome coronavirus vaccine, Antivir. Ther. (Lond.)
Liu, Fontanet, Zhang, Zhan, Xin et al., Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome, J. Infect. Dis
Matsuyama, Nagata, Shirato, Kawase, Takeda et al., Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2, J. Virol
Menachery, Dinnon, Iii, Yount, Jr et al., Trypsin treatment unlocks barrier for zoonotic bat coronaviruses infection, J. Virol, doi:10.1128/JVI.01774-19
Mta, ). EXPERIMANTAL MODEL AND SUBJECT DETAILS Cell cultures, primary cells
Munster, Koopmans, Van Doremalen, Van Riel, De Wit, None
Park, Li, Barlan, Fehr, Perlman et al., Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism
Park, Walls, Wang, Sauer, Li et al., Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors, Nat. Struct. Mol. Biol
Raj, Mou, Smits, Dekkers, Mu ¨ller et al., Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan, Hum. Pathol
Shirato, Kanou, Kawase, Matsuyama, Clinical Isolates of Human Coronavirus 229E Bypass the Endosome for Cell Entry, J. Virol, doi:10.1128/JVI.01387-16
Shirato, Kawase, Matsuyama, Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry, Virology
Shulla, Heald-Sargent, Subramanya, Zhao, Perlman et al., A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, J. Virol
Simmons, Gosalia, Rennekamp, Reeves, Diamond et al., Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry, Proc. Natl. Acad. Sci
Wang, Horby, Hayden, Gao, Summary of probable SARS cases with onset of illness from 1, Lancet
Who, Novel Coronavirus(2019-nCoV) Situation Report 23
Wu, Yang, Beineke, Dijkman, Matrosovich et al., The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells, Sci. Rep
Wu, brief, tissue with a length of approximately 10 mm and a diameter of 8mm was collected and incubated for 24 h at 4 C with DMEM (GIBCO) containing 1 mg/mL protease type XIV and 10 mg/mL DNase I, 100 units/mL penicillin and 100 mg/mL streptomycin, 2.5 mg/mL amphotericin B, and 50 mg/mL gentamicin (GIBCO). The epithelial cells were then harvested from the mucosal surface using the scalpel and were resuspended in growth medium. After incubation at 37 C, 5% CO 2 for 2 h to remove adherent fibroblast cells, non-adherent cells were seeded on a collagen I coated flask and maintained at 37 C, 5% CO 2 . The growth medium was refreshed every 2 days and consisted of a 1:1 mixture of DMEM (GIBCO) and Airway Epithelial Cell basal medium (Promocell, Heidelberg, Germany) supplemented with 52 mg/mL bovine pituitary extract, 15 ng/mL retinoic acid, 5mg/mL insulin, 0.5 mg/mL hydrocortisone, 0.5 mg/mL epinephrine, 10 mg/mL transferrin, 1 ng/mL human epidermal growth factor (Corning), 1.5 ng/mL bovine serum albumin, 100 units/mL penicillin and 100 mg/mL streptomycin, with or without 5 mM Rho-associated protein kinase inhibitor
Yamamoto, Matsuyama, Li, Takeda, Kawaguchi et al., Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay. Antimicrob, Agents Chemother
Yang, Du, Liu, Wang, Ma et al., Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus
Yang, Liu, Du, Jiang, Shi et al., Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus, J. Virol
Yeager, Ashmun, Williams, Cardellichio, Shapiro et al., Human aminopeptidase N is a receptor for human coronavirus 229E, Nature
Zhou, Vedantham, Lu, Agudelo, Carrion et al., Protease inhibitors targeting coronavirus and filovirus entry, Antiviral Res
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, doi:10.1038/s41586-020-2012-7
Zhu, Zhang, Wang, Li, Yang et al., A Novel Coronavirus from Patients with Pneumonia in China, 2019, N Engl J Med
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'2002', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib5', 'doi-asserted-by': 'crossref', 'first-page': 'e0189073', 'DOI': '10.1371/journal.pone.0189073', 'article-title': 'The glycoprotein of vesicular stomatitis virus promotes release of ' 'virus-like particles from tetherin-positive cells', 'volume': '12', 'author': 'Brinkmann', 'year': '2017', 'journal-title': 'PLoS ONE'}, { 'key': '10.1016/j.cell.2020.02.052_bib6', 'doi-asserted-by': 'crossref', 'first-page': '20406', 'DOI': '10.2807/ese.18.08.20406-en', 'article-title': 'Contact investigation of a case of human novel coronavirus infection ' 'treated in a German hospital, October-November 2012', 'volume': '18', 'author': 'Buchholz', 'year': '2013', 'journal-title': 'Euro Surveill.'}, { 'key': '10.1016/j.cell.2020.02.052_bib7', 'doi-asserted-by': 'crossref', 'first-page': '514', 'DOI': '10.1016/S0140-6736(20)30154-9', 'article-title': 'A familial cluster of pneumonia associated with the 2019 novel ' 'coronavirus indicating person-to-person transmission: a study of a ' 'family cluster', 'volume': '395', 'author': 'Chan', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '10.1016/j.cell.2020.02.052_bib8', 'doi-asserted-by': 'crossref', 'first-page': '1136', 'DOI': '10.1007/s00108-019-00671-5', 'article-title': '[Coronaviruses as the cause of respiratory infections]', 'volume': '60', 'author': 'Corman', 'year': '2019', 'journal-title': 'Internist (Berl.)'}, { 'key': '10.1016/j.cell.2020.02.052_bib9', 'doi-asserted-by': 'crossref', 'DOI': '10.2807/1560-7917.ES.2020.25.3.2000045', 'article-title': 'Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR', 'volume': '25', 'author': 'Corman', 'year': '2020', 'journal-title': 'Euro Surveill.'}, { 'key': '10.1016/j.cell.2020.02.052_bib10', 'doi-asserted-by': 'crossref', 'first-page': '523', 'DOI': '10.1038/nrmicro.2016.81', 'article-title': 'SARS and MERS: recent insights into emerging coronaviruses', 'volume': '14', 'author': 'de Wit', 'year': '2016', 'journal-title': 'Nat. Rev. Microbiol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib11', 'doi-asserted-by': 'crossref', 'first-page': '622', 'DOI': '10.1002/path.1560', 'article-title': 'Organ distribution of severe acute respiratory syndrome (SARS) ' 'associated coronavirus (SARS-CoV) in SARS patients: implications for ' 'pathogenesis and virus transmission pathways', 'volume': '203', 'author': 'Ding', 'year': '2004', 'journal-title': 'J.\xa0Pathol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib12', 'doi-asserted-by': 'crossref', 'first-page': '387', 'DOI': '10.1146/annurev-med-051215-031152', 'article-title': 'Middle East Respiratory Syndrome: Emergence of a Pathogenic Human ' 'Coronavirus', 'volume': '68', 'author': 'Fehr', 'year': '2017', 'journal-title': 'Annu. Rev. Med.'}, { 'key': '10.1016/j.cell.2020.02.052_bib13', 'doi-asserted-by': 'crossref', 'first-page': '535', 'DOI': '10.1038/nature12711', 'article-title': 'Isolation and characterization of a bat SARS-like coronavirus that uses ' 'the ACE2 receptor', 'volume': '503', 'author': 'Ge', 'year': '2013', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib14', 'doi-asserted-by': 'crossref', 'first-page': '5502', 'DOI': '10.1128/JVI.00128-13', 'article-title': 'The spike protein of the emerging betacoronavirus EMC uses a novel ' 'coronavirus receptor for entry, can be activated by TMPRSS2, and is ' 'targeted by neutralizing antibodies', 'volume': '87', 'author': 'Gierer', 'year': '2013', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib15', 'doi-asserted-by': 'crossref', 'first-page': '4122', 'DOI': '10.1128/JVI.02232-10', 'article-title': 'Evidence that TMPRSS2 activates the severe acute respiratory syndrome ' 'coronavirus spike protein for membrane fusion and reduces viral control ' 'by the humoral immune response', 'volume': '85', 'author': 'Glowacka', 'year': '2011', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib16', 'doi-asserted-by': 'crossref', 'first-page': '415', 'DOI': '10.1084/jem.20050828', 'article-title': 'Multiple organ infection and the pathogenesis of SARS', 'volume': '202', 'author': 'Gu', 'year': '2005', 'journal-title': 'J.\xa0Exp. Med.'}, { 'key': '10.1016/j.cell.2020.02.052_bib17', 'doi-asserted-by': 'crossref', 'first-page': '276', 'DOI': '10.1126/science.1087139', 'article-title': 'Isolation and characterization of viruses related to the SARS ' 'coronavirus from animals in southern China', 'volume': '302', 'author': 'Guan', 'year': '2003', 'journal-title': 'Science'}, { 'key': '10.1016/j.cell.2020.02.052_bib18', 'doi-asserted-by': 'crossref', 'first-page': '7809', 'DOI': '10.1073/pnas.0711241105', 'article-title': 'Modulation of TNF-alpha-converting enzyme by the spike protein of ' 'SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral ' 'entry', 'volume': '105', 'author': 'Haga', 'year': '2008', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib19', 'doi-asserted-by': 'crossref', 'first-page': '631', 'DOI': '10.1002/path.1570', 'article-title': 'Tissue distribution of ACE2 protein, the functional receptor for SARS ' 'coronavirus. A first step in understanding SARS pathogenesis', 'volume': '203', 'author': 'Hamming', 'year': '2004', 'journal-title': 'J.\xa0Pathol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib20', 'doi-asserted-by': 'crossref', 'first-page': '5757', 'DOI': '10.1128/JVI.00083-06', 'article-title': 'Antigenic and immunogenic characterization of recombinant ' 'baculovirus-expressed severe acute respiratory syndrome coronavirus ' 'spike protein: implication for vaccine design', 'volume': '80', 'author': 'He', 'year': '2006', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib21', 'doi-asserted-by': 'crossref', 'first-page': 'e72942', 'DOI': '10.1371/journal.pone.0072942', 'article-title': 'Differential sensitivity of bat cells to infection by enveloped RNA ' 'viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza ' 'viruses', 'volume': '8', 'author': 'Hoffmann', 'year': '2013', 'journal-title': 'PLoS ONE'}, { 'key': '10.1016/j.cell.2020.02.052_bib22', 'doi-asserted-by': 'crossref', 'first-page': '1216', 'DOI': '10.1016/j.bbrc.2004.05.114', 'article-title': 'Susceptibility to SARS coronavirus S protein-driven infection ' 'correlates with expression of angiotensin converting enzyme 2 and ' 'infection can be blocked by soluble receptor', 'volume': '319', 'author': 'Hofmann', 'year': '2004', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': '10.1016/j.cell.2020.02.052_bib23', 'doi-asserted-by': 'crossref', 'first-page': '6134', 'DOI': '10.1128/JVI.78.12.6134-6142.2004', 'article-title': 'S protein of severe acute respiratory syndrome-associated coronavirus ' 'mediates entry into hepatoma cell lines and is targeted by neutralizing ' 'antibodies in infected patients', 'volume': '78', 'author': 'Hofmann', 'year': '2004', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib24', 'doi-asserted-by': 'crossref', 'first-page': '7988', 'DOI': '10.1073/pnas.0409465102', 'article-title': 'Human coronavirus NL63 employs the severe acute respiratory syndrome ' 'coronavirus receptor for cellular entry', 'volume': '102', 'author': 'Hofmann', 'year': '2005', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib25', 'series-title': 'Clinical features of patients infected with 2019 novel coronavirus in ' 'Wuhan', 'author': 'Huang', 'year': '2020'}, { 'key': '10.1016/j.cell.2020.02.052_bib26', 'doi-asserted-by': 'crossref', 'first-page': '112', 'DOI': '10.1038/nature03712', 'article-title': 'Angiotensin-converting enzyme 2 protects from severe acute lung failure', 'volume': '436', 'author': 'Imai', 'year': '2005', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib27', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/JVI.01815-18', 'article-title': 'TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways ' 'of Murine Models after Coronavirus Infection', 'volume': '93', 'author': 'Iwata-Yoshikawa', 'year': '2019', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib28', 'doi-asserted-by': 'crossref', 'first-page': '6537', 'DOI': '10.1128/JVI.00094-12', 'article-title': 'Simultaneous treatment of human bronchial epithelial cells with serine ' 'and cysteine protease inhibitors prevents severe acute respiratory ' 'syndrome coronavirus entry', 'volume': '86', 'author': 'Kawase', 'year': '2012', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib29', 'doi-asserted-by': 'crossref', 'first-page': '965', 'DOI': '10.1128/MCB.26.3.965-975.2006', 'article-title': 'Phenotypic analysis of mice lacking the Tmprss2-encoded protease', 'volume': '26', 'author': 'Kim', 'year': '2006', 'journal-title': 'Mol. Cell. Biol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib30', 'doi-asserted-by': 'crossref', 'first-page': '16597', 'DOI': '10.1038/s41598-018-34859-w', 'article-title': 'Functional analysis of potential cleavage sites in the MERS-coronavirus ' 'spike protein', 'volume': '8', 'author': 'Kleine-Weber', 'year': '2018', 'journal-title': 'Sci. Rep.'}, { 'key': '10.1016/j.cell.2020.02.052_bib31', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/JVI.01381-18', 'article-title': 'Mutations in the Spike Protein of Middle East Respiratory Syndrome ' 'Coronavirus Transmitted in Korea Increase Resistance to ' 'Antibody-Mediated Neutralization', 'volume': '93', 'author': 'Kleine-Weber', 'year': '2019', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib32', 'doi-asserted-by': 'crossref', 'first-page': '875', 'DOI': '10.1038/nm1267', 'article-title': 'A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS ' 'coronavirus-induced lung injury', 'volume': '11', 'author': 'Kuba', 'year': '2005', 'journal-title': 'Nat. Med.'}, { 'key': '10.1016/j.cell.2020.02.052_bib62', 'doi-asserted-by': 'crossref', 'first-page': '1547', 'DOI': '10.1093/molbev/msy096', 'article-title': 'MEGA X: Molecular Evolutionary Genetics Analysis across Computing ' 'Platforms', 'volume': '35', 'author': 'Kumar', 'year': '2018', 'journal-title': 'Mol Biol Evol'}, { 'key': '10.1016/j.cell.2020.02.052_bib33', 'doi-asserted-by': 'crossref', 'first-page': '14040', 'DOI': '10.1073/pnas.0506735102', 'article-title': 'Severe acute respiratory syndrome coronavirus-like virus in Chinese ' 'horseshoe bats', 'volume': '102', 'author': 'Lau', 'year': '2005', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib34', 'doi-asserted-by': 'crossref', 'first-page': '450', 'DOI': '10.1038/nature02145', 'article-title': 'Angiotensin-converting enzyme 2 is a functional receptor for the SARS ' 'coronavirus', 'volume': '426', 'author': 'Li', 'year': '2003', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib35', 'doi-asserted-by': 'crossref', 'first-page': '1864', 'DOI': '10.1126/science.1116480', 'article-title': 'Structure of SARS coronavirus spike receptor-binding domain complexed ' 'with receptor', 'volume': '309', 'author': 'Li', 'year': '2005', 'journal-title': 'Science'}, { 'key': '10.1016/j.cell.2020.02.052_bib36', 'doi-asserted-by': 'crossref', 'first-page': '1634', 'DOI': '10.1038/sj.emboj.7600640', 'article-title': 'Receptor and viral determinants of SARS-coronavirus adaptation to human ' 'ACE2', 'volume': '24', 'author': 'Li', 'year': '2005', 'journal-title': 'EMBO J.'}, { 'key': '10.1016/j.cell.2020.02.052_bib37', 'doi-asserted-by': 'crossref', 'first-page': 'E8508', 'DOI': '10.1073/pnas.1712592114', 'article-title': 'Identification of sialic acid-binding function for the Middle East ' 'respiratory syndrome coronavirus spike glycoprotein', 'volume': '114', 'author': 'Li', 'year': '2017', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib38', 'doi-asserted-by': 'crossref', 'first-page': '1107', 'DOI': '10.1177/135965350701200702', 'article-title': 'Safety and immunogenicity from a phase I trial of inactivated severe ' 'acute respiratory syndrome coronavirus vaccine', 'volume': '12', 'author': 'Lin', 'year': '2007', 'journal-title': 'Antivir. Ther. (Lond.)'}, { 'key': '10.1016/j.cell.2020.02.052_bib39', 'doi-asserted-by': 'crossref', 'first-page': '792', 'DOI': '10.1086/500469', 'article-title': 'Two-year prospective study of the humoral immune response of patients ' 'with severe acute respiratory syndrome', 'volume': '193', 'author': 'Liu', 'year': '2006', 'journal-title': 'J.\xa0Infect. Dis.'}, { 'key': '10.1016/j.cell.2020.02.052_bib40', 'doi-asserted-by': 'crossref', 'first-page': '12658', 'DOI': '10.1128/JVI.01542-10', 'article-title': 'Efficient activation of the severe acute respiratory syndrome ' 'coronavirus spike protein by the transmembrane protease TMPRSS2', 'volume': '84', 'author': 'Matsuyama', 'year': '2010', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib41', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/JVI.01774-19', 'article-title': 'Trypsin treatment unlocks barrier for zoonotic bat coronaviruses ' 'infection', 'volume': '94', 'author': 'Menachery', 'year': '2020', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib42', 'doi-asserted-by': 'crossref', 'first-page': '692', 'DOI': '10.1056/NEJMp2000929', 'article-title': 'A Novel Coronavirus Emerging in China - Key Questions for Impact ' 'Assessment', 'volume': '382', 'author': 'Munster', 'year': '2020', 'journal-title': 'N.\xa0Engl. J. Med.'}, { 'key': '10.1016/j.cell.2020.02.052_bib43', 'doi-asserted-by': 'crossref', 'first-page': '12262', 'DOI': '10.1073/pnas.1608147113', 'article-title': 'Proteolytic processing of Middle East respiratory syndrome coronavirus ' 'spikes expands virus tropism', 'volume': '113', 'author': 'Park', 'year': '2016', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib44', 'doi-asserted-by': 'crossref', 'first-page': '1151', 'DOI': '10.1038/s41594-019-0334-7', 'article-title': 'Structures of MERS-CoV spike glycoprotein in complex with sialoside ' 'attachment receptors', 'volume': '26', 'author': 'Park', 'year': '2019', 'journal-title': 'Nat. Struct. Mol. Biol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib45', 'doi-asserted-by': 'crossref', 'first-page': '251', 'DOI': '10.1038/nature12005', 'article-title': 'Dipeptidyl peptidase 4 is a functional receptor for the emerging human ' 'coronavirus-EMC', 'volume': '495', 'author': 'Raj', 'year': '2013', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib46', 'doi-asserted-by': 'crossref', 'first-page': '303', 'DOI': '10.1016/j.humpath.2004.11.006', 'article-title': 'Immunohistochemical, in\xa0situ hybridization, and ultrastructural ' 'localization of SARS-associated coronavirus in lung of a fatal case of ' 'severe acute respiratory syndrome in Taiwan', 'volume': '36', 'author': 'Shieh', 'year': '2005', 'journal-title': 'Hum. Pathol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib47', 'article-title': 'Clinical Isolates of Human Coronavirus 229E Bypass the Endosome for ' 'Cell Entry', 'volume': '91', 'author': 'Shirato', 'year': '2016', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib48', 'doi-asserted-by': 'crossref', 'first-page': '9', 'DOI': '10.1016/j.virol.2017.11.012', 'article-title': 'Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal ' 'cathepsins for cell entry', 'volume': '517', 'author': 'Shirato', 'year': '2018', 'journal-title': 'Virology'}, { 'key': '10.1016/j.cell.2020.02.052_bib49', 'doi-asserted-by': 'crossref', 'first-page': '873', 'DOI': '10.1128/JVI.02062-10', 'article-title': 'A transmembrane serine protease is linked to the severe acute ' 'respiratory syndrome coronavirus receptor and activates virus entry', 'volume': '85', 'author': 'Shulla', 'year': '2011', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib50', 'doi-asserted-by': 'crossref', 'first-page': '11876', 'DOI': '10.1073/pnas.0505577102', 'article-title': 'Inhibitors of cathepsin L prevent severe acute respiratory syndrome ' 'coronavirus entry', 'volume': '102', 'author': 'Simmons', 'year': '2005', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib51', 'doi-asserted-by': 'crossref', 'first-page': '470', 'DOI': '10.1016/S0140-6736(20)30185-9', 'article-title': 'A novel coronavirus outbreak of global health concern', 'volume': '395', 'author': 'Wang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '10.1016/j.cell.2020.02.052_bib52', 'series-title': 'Summary of probable SARS cases with onset of illness from 1 November ' '2002 to 31 July 2003', 'year': '2004'}, { 'key': '10.1016/j.cell.2020.02.052_bib53', 'series-title': 'Novel Coronavirus(2019-nCoV) Situation Report 23', 'year': '2020'}, { 'key': '10.1016/j.cell.2020.02.052_bib54', 'doi-asserted-by': 'crossref', 'first-page': '39668', 'DOI': '10.1038/srep39668', 'article-title': 'The differentiated airway epithelium infected by influenza viruses ' 'maintains the barrier function despite a dramatic loss of ciliated ' 'cells', 'volume': '6', 'author': 'Wu', 'year': '2016', 'journal-title': 'Sci. Rep.'}, { 'key': '10.1016/j.cell.2020.02.052_bib55', 'doi-asserted-by': 'crossref', 'first-page': '6532', 'DOI': '10.1128/AAC.01043-16', 'article-title': 'Identification of Nafamostat as a Potent Inhibitor of Middle East ' 'Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion ' 'Using the Split-Protein-Based Cell-Cell Fusion Assay', 'volume': '60', 'author': 'Yamamoto', 'year': '2016', 'journal-title': 'Antimicrob. Agents Chemother.'}, { 'key': '10.1016/j.cell.2020.02.052_bib56', 'doi-asserted-by': 'crossref', 'first-page': '12516', 'DOI': '10.1073/pnas.1405889111', 'article-title': 'Receptor usage and cell entry of bat coronavirus HKU4 provide insight ' 'into bat-to-human transmission of MERS coronavirus', 'volume': '111', 'author': 'Yang', 'year': '2014', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': '10.1016/j.cell.2020.02.052_bib57', 'doi-asserted-by': 'crossref', 'first-page': '9119', 'DOI': '10.1128/JVI.01279-15', 'article-title': 'Two Mutations Were Critical for Bat-to-Human Transmission of Middle ' 'East Respiratory Syndrome Coronavirus', 'volume': '89', 'author': 'Yang', 'year': '2015', 'journal-title': 'J.\xa0Virol.'}, { 'key': '10.1016/j.cell.2020.02.052_bib58', 'doi-asserted-by': 'crossref', 'first-page': '420', 'DOI': '10.1038/357420a0', 'article-title': 'Human aminopeptidase N is a receptor for human coronavirus 229E', 'volume': '357', 'author': 'Yeager', 'year': '1992', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib59', 'doi-asserted-by': 'crossref', 'first-page': '76', 'DOI': '10.1016/j.antiviral.2015.01.011', 'article-title': 'Protease inhibitors targeting coronavirus and filovirus entry', 'volume': '116', 'author': 'Zhou', 'year': '2015', 'journal-title': 'Antiviral Res.'}, { 'key': '10.1016/j.cell.2020.02.052_bib60', 'doi-asserted-by': 'crossref', 'DOI': '10.1038/s41586-020-2951-z', 'article-title': 'A pneumonia outbreak associated with a new coronavirus of probable bat ' 'origin', 'author': 'Zhou', 'year': '2020', 'journal-title': 'Nature'}, { 'key': '10.1016/j.cell.2020.02.052_bib61', 'doi-asserted-by': 'crossref', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'article-title': 'A Novel Coronavirus from Patients with Pneumonia in China, 2019', 'volume': '382', 'author': 'Zhu', 'year': '2020', 'journal-title': 'N Engl J Med.'}], 'container-title': 'Cell', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0092867420302294?httpAccept=text/xml', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://api.elsevier.com/content/article/PII:S0092867420302294?httpAccept=text/plain', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2024, 4, 5]], 'date-time': '2024-04-05T18:47:03Z', 'timestamp': 1712342823000}, 'score': 1, 'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S0092867420302294'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 4]]}, 'references-count': 62, 'journal-issue': {'issue': '2', 'published-print': {'date-parts': [[2020, 4]]}}, 'alternative-id': ['S0092867420302294'], 'URL': 'http://dx.doi.org/10.1016/j.cell.2020.02.052', 'relation': { 'has-review': [ { 'id-type': 'doi', 'id': '10.3410/f.737494462.793573238', 'asserted-by': 'object'}, { 'id-type': 'doi', 'id': '10.3410/f.737494462.793581925', 'asserted-by': 'object'}, { 'id-type': 'doi', 'id': '10.3410/f.737494462.793575061', 'asserted-by': 'object'}, { 'id-type': 'doi', 'id': '10.3410/f.737494462.793573616', 'asserted-by': 'object'}], 'has-preprint': [ { 'id-type': 'doi', 'id': '10.1101/2020.01.31.929042', 'asserted-by': 'object'}]}, 'ISSN': ['0092-8674'], 'subject': [], 'container-title-short': 'Cell', 'published': {'date-parts': [[2020, 4]]}, 'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'}, { 'value': 'SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a ' 'Clinically Proven Protease Inhibitor', 'name': 'articletitle', 'label': 'Article Title'}, {'value': 'Cell', 'name': 'journaltitle', 'label': 'Journal Title'}, { 'value': 'https://doi.org/10.1016/j.cell.2020.02.052', 'name': 'articlelink', 'label': 'CrossRef DOI link to publisher maintained version'}, {'value': 'article', 'name': 'content_type', 'label': 'Content Type'}, {'value': '© 2020 Elsevier Inc.', 'name': 'copyright', 'label': 'Copyright'}]}
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