{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:42:22Z","timestamp":1790692942511,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Organization for Scientific Research","award":["016.VICI.170.090"],"award-info":[{"award-number":["016.VICI.170.090"]}]},{"name":"Human Frontiers Science Program","award":["RGP0007\/2017"],"award-info":[{"award-number":["RGP0007\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.<\/jats:p>","DOI":"10.3390\/v13020282","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T18:46:31Z","timestamp":1613155591000},"page":"282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro"],"prefix":"10.3390","volume":"13","author":[{"given":"Finny","family":"Varghese","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-6649","authenticated-orcid":false,"given":"Esther","family":"van Woudenbergh","sequence":"additional","affiliation":[{"name":"Section Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"},{"name":"Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, 3721 MA Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8356-8165","authenticated-orcid":false,"given":"Gijs","family":"Overheul","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7454-018X","authenticated-orcid":false,"given":"Marc","family":"Eleveld","sequence":"additional","affiliation":[{"name":"Section Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Kurver","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"van Heerbeek","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Radboudumc, 6500 HB Nijmegen, The 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marien","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Section Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0221-4689","authenticated-orcid":false,"given":"Ronald","family":"van Rij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2006.01.017","article-title":"Nidovirales: Evolving the largest RNA virus genome","volume":"117","author":"Gorbalenya","year":"2006","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.1118391","article-title":"Bats Are Natural Reservoirs of SARS-Like Coronaviruses","volume":"310","author":"Li","year":"2005","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1128\/JVI.80.9.4211-4219.2006","article-title":"Animal Origins of the Severe Acute Respiratory Syndrome Coronavirus: Insight from ACE2-S-Protein Interactions","volume":"80","author":"Li","year":"2006","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12985-016-0544-0","article-title":"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir","volume":"13","author":"Mohd","year":"2016","journal-title":"Virol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1038\/s41467-020-18272-4","article-title":"Substantial underestimation of SARS-CoV-2 infection in the United States","volume":"11","author":"Wu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_9","first-page":"101212","article-title":"Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1\/S2 Site","volume":"23","author":"Jaimes","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104742","DOI":"10.1016\/j.antiviral.2020.104742","article-title":"The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade","volume":"176","author":"Coutard","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8722","DOI":"10.1128\/JVI.00253-07","article-title":"Clathrin-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus into Target Cells Expressing ACE2 with the Cytoplasmic Tail Deleted","volume":"81","author":"Inoue","year":"2007","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Burkard, C., Verheije, M.H., Wicht, O., van Kasteren, S.I., van Kuppeveld, F.J., Haagmans, B.L., Pelkmans, L., Rottier, P.J.M., Bosch, B.J., and de Haan, C.A.M. (2014). Coronavirus Cell Entry Occurs through the Endo-\/Lysosomal Pathway in a Proteolysis-Dependent Manner. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004502"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41586-020-2575-3","article-title":"Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2","volume":"585","author":"Hoffmann","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"V\u2019Kovski, P., Kratzel, A., Steiner, S., Stalder, H., and Thiel, V. (2020). Coronavirus biology and replication: Implications for SARS-CoV-2. Nat. Rev. Microbiol., epub ahead of print.","DOI":"10.1038\/s41579-020-00468-6"},{"key":"ref_17","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":"Falzarano","year":"2016","journal-title":"Nat. Rev. Microbiol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review","volume":"324","author":"Wiersinga","year":"2020","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","article-title":"SARS-CoV-2 vaccines in development","volume":"586","author":"Krammer","year":"2020","journal-title":"Nature"},{"key":"ref_20","unstructured":"RECOVERY Collaborative Group, Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., and Ustianowski, A. (2020). Dexamethasone in Hospitalized Patients with Covid-19-Preliminary Report. N. Engl. J. Med., epub ahead of print."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1128\/AAC.02427-14","article-title":"Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-\u03baB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication","volume":"58","author":"Song","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12985-016-0674-4","article-title":"Berberine inhibits enterovirus 71 replication by downregulating the MEK\/ERK signaling pathway and autophagy","volume":"14","author":"Wang","year":"2017","journal-title":"Virol. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9743","DOI":"10.1128\/JVI.01382-16","article-title":"The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling","volume":"90","author":"Varghese","year":"2016","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e02227-16","DOI":"10.1128\/AAC.02227-16","article-title":"Obatoclax Inhibits Alphavirus Membrane Fusion by Neutralizing the Acidic Environment of Endocytic Compartments","volume":"61","author":"Varghese","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Andersen, P.I., Krpina, K., Ianevski, A., Shtaida, N., Jo, E., Yang, J., Koit, S., Tenson, T., Hukkanen, V., and Anthonsen, M.W. (2019). Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine. Viruses, 11.","DOI":"10.20944\/preprints201909.0128.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01987-20","DOI":"10.1128\/JVI.01987-20","article-title":"Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives","volume":"95","author":"Tandon","year":"2021","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wolters, F., Coolen, J.P.M., Tostmann, A., van Groningen, L.F.J., Bleeker-Rovers, C.P., Tan, E.C.T.H., van der Geest-Blankert, N., Hautvast, J.L.A., Hopman, J., and Wertheim, H.F.L. (2020). Novel SARS-CoV-2 Whole-genome sequencing technique using Reverse Complement PCR enables easy, fast and accurate outbreak analysis in hospital and community settings. bioRxiv.","DOI":"10.1101\/2020.10.29.360578"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41564-020-0770-5","article-title":"A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology","volume":"5","author":"Rambaut","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_29","first-page":"68","article-title":"Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein","volume":"12","author":"Davidson","year":"2020","journal-title":"Gen. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1099\/jgv.0.001453","article-title":"SARS-coronavirus-2 replication in Vero E6 cells: Replication kinetics, rapid adaptation and cytopathology","volume":"101","author":"Ogando","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1099\/0022-1317-43-1-247","article-title":"Regulation of the Interferon System\u2014Evidence That Vero Cells Have a Genetic Defect in Interferon-Production","volume":"43","author":"Emeny","year":"1979","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8942","DOI":"10.1128\/JVI.00676-08","article-title":"Efficient multiplication of human metapneumovirus in Vero cells expressing the transmembrane serine protease TMPRSS2","volume":"82","author":"Shirogane","year":"2008","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12985-016-0479-5","article-title":"Coronaviruses and the human airway: A universal system for virus-host interaction studies","volume":"13","author":"Jonsdottir","year":"2016","journal-title":"Virol. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1128\/jvi.67.7.4274-4282.1993","article-title":"Vectorial release of poliovirus from polarized human intestinal epithelial cells","volume":"67","author":"Tucker","year":"1993","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12026","DOI":"10.1128\/JVI.02048-15","article-title":"Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System","volume":"89","author":"Katoh","year":"2015","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9470","DOI":"10.1128\/JVI.79.15.9470-9479.2005","article-title":"Apical entry and release of severe acute respiratory syndrome-associated coronavirus in polarized Calu-3 lung epithelial cells","volume":"79","author":"Tseng","year":"2005","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lenzen, M., Li, M., Malik, A., Pomponi, F., Sun, Y.-Y., Wiedmann, T., Faturay, F., Fry, J., Gallego, B., and Geschke, A. (2020). Global socio-economic losses and environmental gains from the Coronavirus pandemic. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235654"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3389\/fphar.2018.00557","article-title":"Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders","volume":"9","author":"Neag","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24748","DOI":"10.1038\/srep24748","article-title":"Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections","volume":"6","author":"Chu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s11684-019-0724-6","article-title":"Biological properties and clinical applications of berberine","volume":"14","author":"Song","year":"2020","journal-title":"Front. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e7697","DOI":"10.1097\/MD.0000000000007697","article-title":"Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial","volume":"96","author":"Zhang","year":"2017","journal-title":"Medicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ejphar.2015.05.068","article-title":"Current knowledge and pharmacological profile of berberine: An update","volume":"761","author":"Kumar","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1007\/s00705-020-04706-3","article-title":"Antiviral activity of berberine","volume":"165","author":"Warowicka","year":"2020","journal-title":"Arch. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104878","DOI":"10.1016\/j.antiviral.2020.104878","article-title":"In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2","volume":"181","author":"Pizzorno","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.antiviral.2015.12.012","article-title":"Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses","volume":"126","author":"Varghese","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e01382-20","DOI":"10.1128\/mBio.01382-20","article-title":"Berberine Chloride is an Alphavirus Inhibitor That Targets Nucleocapsid Assembly","volume":"11","author":"Wan","year":"2020","journal-title":"mBio"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Farooqi, A.A., Qureshi, M.Z., Khalid, S., Attar, R., Martinelli, C., Sabitaliyevich, U.Y., Nurmurzayevich, S.B., Taverna, S., Poltronieri, P., and Xu, B. (2019). Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11040478"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"708292","DOI":"10.1100\/2012\/708292","article-title":"Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine","volume":"2012","author":"Chen","year":"2012","journal-title":"Sci. World J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1515\/BC.2008.145","article-title":"RNA viruses and the mitogenic Raf\/MEK\/ERK signal transduction cascade","volume":"389","author":"Stephan","year":"2008","journal-title":"Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.cell.2020.06.034","article-title":"The Global Phosphorylation Landscape of SARS-CoV-2 Infection","volume":"182","author":"Bouhaddou","year":"2020","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19512","DOI":"10.1073\/pnas.0709443104","article-title":"Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis","volume":"104","author":"Nguyen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/CE.S42568","article-title":"An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies","volume":"8","author":"Goard","year":"2013","journal-title":"Core Evid."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1158\/1078-0432.CCR-10-0822","article-title":"Phase I Dose Finding Studies of Obatoclax (GX15-070), a Small Molecule Pan-BCL-2 Family Antagonist, in Patients with Advanced Solid Tumors or Lymphoma","volume":"16","author":"Hwang","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.3109\/10428194.2015.1048441","article-title":"Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia","volume":"56","author":"Brown","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/bjc.2012.21","article-title":"A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer","volume":"106","author":"Chiappori","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Schimmer, A.D., Raza, A., Carter, T.H., Claxton, D., Erba, H., DeAngelo, D.J., Tallman, M.S., Goard, C., and Borthakur, G. (2014). A multicenter phase I\/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108694"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.lungcan.2014.05.003","article-title":"Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer","volume":"85","author":"Langer","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ianevski, A., Yao, R., Fenstad, M.H., Biza, S., Zusinaite, E., Reisberg, T., Lysvand, H., Loseth, K., Landsem, V.M., and Malmring, J.F. (2020). Potential Antiviral Options against SARS-CoV-2 Infection. Viruses, 12.","DOI":"10.1101\/2020.05.12.091165"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Dittmar, M., Lee, J.S., Whig, K., Segrist, E., Li, M., Jurado, K., Samby, K., Ramage, H., Schultz, D., and Cherry, S. (2020). Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2. bioRxiv.","DOI":"10.1101\/2020.06.19.161042"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1038\/s41467-020-17796-z","article-title":"Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells","volume":"11","author":"Zhu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100059","DOI":"10.1016\/j.xcrm.2020.100059","article-title":"Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia","volume":"1","author":"Pizzorno","year":"2020","journal-title":"Cell Rep. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1164\/ajrccm.160.supplement_1.11","article-title":"Airway epithelial cells, cytokines, and pollutants","volume":"160","author":"Mills","year":"1999","journal-title":"Am. J. Resp. Crit. Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/biof.19","article-title":"Type III IFNs: New layers of complexity in innate antiviral immunity","volume":"35","author":"Ank","year":"2009","journal-title":"Biofactors"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1128\/CMR.00014-10","article-title":"The airway epithelium: Soldier in the fight against respiratory viruses","volume":"24","author":"Vareille","year":"2011","journal-title":"Clin. Microbiol. 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