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Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
Depfenhart et al., Internal and Emergency Medicine, doi:10.1007/s11739-020-02383-3 (Theory)
Depfenhart et al., Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?, Internal and Emergency Medicine, doi:10.1007/s11739-020-02383-3 (Theory)
May 2020   Source   PDF  
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Proposal to use bromhexine to inhibit TMPRSS2-specific viral entry for prophylaxis and treatment of COVID-19.
Depfenhart et al., 26 May 2020, peer-reviewed, 5 authors.
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Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
Markus Depfenhart, Danielle De Villiers, Gottfried Lemperle, Markus Meyer, Salvatore Di Somma
Internal and Emergency Medicine, doi:10.1007/s11739-020-02383-3
Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide.
Author contributions The authors wish it to be known that, in their opinion, the first two authors (MD and DdV) should be regarded as joint first authors. MD contributed to writing the article, literature research, and proposed the drug based on the criteria discussed in the article. DdV contributed to writing the article, literature research, and contributed the illustrations. GL contributed literature research, additional writing, advise, and context. MM contributed literature research, additional writing, advise, and context. SDS contributed literature research, additional writing, advise, and context. Ethical approval No ethics approval is required. Consent to participate This article does not contain any study with humans performed by any of the authors. Consent for publication No informed consent is required. Code availability Not applicable.
Agostini, Andres, Sims, Graham, Sheahan et al., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease, mBio, doi:10.1128/mBio.00221-18
Aguiar, Murce, Cortopassi, Pimentel, Almeida et al., Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity, Int J Parasitol Drugs Drug Resist, doi:10.1016/j.ijpddr.2018.10.002
Belouzard, Millet, Licitra, Whittaker, Mechanisms of coronavirus cell entry mediated by the viral spike protein, Viruses, doi:10.3390/v4061011
Bottcher-Friebertshauser, Lu, Meyer, Sielaff, Steinmetzer et al., Hemagglutinin activating host cell proteases provide promising drug targets for the treatment of influenza A and B virus infections, Vaccine, doi:10.1016/j.vaccine.2012.10.001
Báez-Santos, John, Mesecar, The SARScoronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds, Antiviral Res, doi:10.1016/j.antiviral.2014.12.015
Cao, Wang, Wen, Liu, Wang, A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19, N Engl J Med, doi:10.1056/NEJMoa2001282
Cascella, Rajnik, Cuomo, Dulebohn, Napoli, Features, evaluation and treatment coronavirus (COVID-19
Chan, Kok, Zhu, Chu, To et al., Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan, Emerg Microbes Infect, doi:10.1080/22221751.2020.1719902
Chang, Cheng, Chang, Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children and adults, Cochrane Database Syst Rev, doi:10.1002/14651858.CD006088.pub2
Chen, Yiu, Wong, Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates, F1000Res, doi:10.1288/f1000research.22457.1
Crackower, Sarao, Oudit, Yagil, Kozieradzki et al., Angiotensin-converting enzyme 2 is an essential regulator of heart function, Nature, doi:10.1038/nature00786
Craven, Regulatory affairs professionals society
Danelius, Andersson, Jarvoll, Lood, Gräfenstein et al., Halogen bonding: a powerful tool for modulation of peptide conformation, Biochemistry, doi:10.1021/acs.biochem.7b00429
Ding, Zhao, Lan, Li, Lv et al., Induction of atypical autophagy by porcine hemagglutinating encephalomyelitis virus contributes to viral replication, Front Cell Infect Microbiol, doi:10.3389/fcimb.2017.00056
Drosten, Gunther, Preiser, Van Der Werf, Brodt et al., Identification of a novel coronavirus in patients with severe acute respiratory syndrome, N Engl J Med, doi:10.1056/NEJMoa030747
Fehr, Perlman, Coronaviruses: an overview of their replication and pathogenesis, Methods Mol Biol, doi:10.1007/978-1-4939-2438-7_1
Frlan, Gobec, Inhibitors of cathepsin B, Curr Med Chem, doi:10.2174/092986706777935122
Gao, Huang, Han, Bai, Wang, The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats, Arch Med Sci, doi:10.5114/aoms.2011.23403
Gattinoni, Chiumello, Caironi, Busana, Romitti et al., COVID-19 pneumonia: different respiratory treatment for different phenotypes?, Intensive Care Med, doi:10.1007/s00134-020-06033-2
Gautret, Lagier, Parola, Hoang, Medded et al., openlabel non-randomized clinical trial, doi:10.1101/2020.03.16.20037135
Golden, Cho, Hofman, Louie, Schonthal et al., Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors, Neurosurg Focus, doi:10.3171/2014.12.FOCUS14748
Good, Shader, Lethality and behavioral side effects of chloroquine, J Clin Psychopharmacol, doi:10.1097/00004714-198202000-00005
Gorbalenya, Baker, Baric, De Groot, Drosten et al., The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol, doi:10.1038/s41564-020-0695-z
Gu, Gong, Zhang, Zheng, Gao et al., Multiple organ infection and the pathogenesis of SARS, J Exp Med, doi:10.1084/jem.20050828
Gulati, Rai, Chaudhary, Ray, Nutraceuticals in respiratory disorders
Han, Mallampalli, The role of surfactant in lung disease and host defense against pulmonary infections, Ann Am Thorac Soc, doi:10.1513/AnnalsATS.201411-507FR
Harcourt, Jukneliene, Kanjanahaluethai, Bechill, Severson et al., Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity, J Virol, doi:10.1128/jvi.78.24.13600-13612.2004
Hashimoto, Perlot, Rehman, Trichereau, Ishiguro et al., ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation, Nature, doi:10.1038/nature11228
Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Holshue, Debolt, Lindquist, Lofy, Wiesman et al., First case of 2019 novel coronavirus in the United States, N Engl J Med, doi:10.1056/NEJMoa2001191
Huynh, Wang, Luan, In silico exploration of the molecular mechanism of clinically oriented drugs for possibly inhibiting SARS-CoV-2's main protease, J Phys Chem Lett, doi:10.1021/acs.jpclett.0c00994
Inglot, Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs, J Gen Virol, doi:10.1099/0022-1317-4-2-203
Jang, Choi, Byun, Jue, Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes, Rheumatology, doi:10.1093/rheumatology/kei282
Keyaerts, Li, Vijgen, Rysman, Verbeeck et al., Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice, Antimicrob Agents Chemother, doi:10.1128/aac.01509-08
Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2004.08.085
Kirchdoerfer, Cottrell, Wang, Pallesen, Yassine et al., Pre-fusion structure of a human coronavirus spike protein, Nature, doi:10.1038/nature17200
Ksiazek, Erdman, Goldsmith, Zaki, Peret et al., A novel coronavirus associated with severe acute respiratory syndrome, N Engl J Med, doi:10.1056/NEJMoa030781
Kuba, Imai, Rao, Gao, Guo et al., A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury, Nat Med, doi:10.1038/nm1267
Laporte, Naesens, Airway proteases: an emerging drug target for influenza and other respiratory virus infections, Curr Opin Virol, doi:10.1016/j.coviro.2017.03.018
Li, Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV), Nat Rev Drug Discov, doi:10.1038/d41573-020-00016-0
Lim, Jeon, Shin, Kim, Seong et al., Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR, J Korean Med Sci, doi:10.3346/jkms.2020.35.e79
Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov, doi:10.1038/s41421-020-0156-0
Lu, Zhao, Li, Niu, Yang et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, Lancet (London, doi:10.1016/S0140-6736(20)30251-8
Lucas, Heinlein, Kim, Hernandez, Malik et al., The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis, Cancer Discov, doi:10.1158/
Mcchesney, Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate, Am J Med, doi:10.1016/0002-9343(83)91265-2
Mikkonen, Pihlajamaa, Sahu, Zhang, Janne, Androgen receptor and androgen-dependent gene expression in lung, Mol Cell Endocrinol, doi:10.1016/j.mce.2009.12.022
Paton, Lee, Xu, Ooi, Cheung et al., Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial, Lancet Infect Dis, doi:10.1016/S1473-3099(11)70065-2
Plomer, De Zeeuw, More than expectorant: new scientific data on ambroxol in the context of the treatment of bronchopulmonary diseases, MMW Fortschritte der Medizin, doi:10.1007/s15006-017-9805-0
Ramsey, Nuttall, Hart, on behalf of the TIT (2019) A phase 1/2 trial to evaluate the pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC), Trials, doi:10.1186/s13063-019-3606-y
Ranieri, Rubenfeld, Thompson, Ferguson, Caldwell, Acute respiratory distress syndrome: the Berlin Definition, JAMA, doi:10.1001/jama.2012.5669
Rubio-Aliaga, Frey, Boll, Groneberg, Eichinger et al., Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney, Mol Cell Biol
Schrezenmeier, Dorner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol, doi:10.1038/s41584-020-0372-x
Shimizu, Yamamoto, Homma, Ishida, Effect of chloroquine on the growth of animal viruses, Archiv für die gesamte Virusforschung, doi:10.1007/BF01250299
Simmons, Zmora, Gierer, Heurich, Pöhlmann, Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research, Antiviral Res, doi:10.1016/j.antiviral.2013.09.028
Tan, Yam, Sun, Chu, An evaluation of chloroquine as a broad-acting antiviral against hand, foot and mouth disease, Antiviral Res, doi:10.1016/j.antiviral.2017.11.017
Touret, De Lamballerie, Of chloroquine and COVID-19, Antiviral Res, doi:10.1016/j.antiviral.2020.104762
Turk, Stoka, Vasiljeva, Renko, Sun et al., Cysteine cathepsins: from structure, function and regulation to new frontiers, Biochem Biophys Acta, doi:10.1016/j.bbapap.2011.10.002
Vincent, Bergeron, Benjannet, Erickson, Rollin et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J, doi:10.1186/1743-422X-2-69
Waldrop, Alsup, Mclaughlin, Fearing coronavirus, Arizona man dies after taking a form of chloroquine used to treat aquariums, CNN Health
Wan, Shang, Graham, Baric, Li, Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS, J Virol, doi:10.1128/jvi.00127-20
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Weniger, Review of side effects and toxicity of chloroquine
Wrapp, Wang, Corbett, Goldsmith, Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, doi:10.1126/science.abb2507
Wu, Zhao, Yu, Chen, Song, A new coronavirus associated with human respiratory disease in China, Nature, doi:10.1038/s41586-020-2008-3
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 cellcell fusion assay, Antimicrob Agents Chemother, doi:10.1128/AAC.01043-16
Yan, Zou, Sun, Li, Xu et al., Antimalaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model, Cell Res, doi:10.1038/cr.2012.165
Yao, Ye, Zhang, Cui, Huang et al., In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis, doi:10.1093/cid/ciaa237
Yeo, Kaushal, Yeo, Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible? Lancet, Gastroenterol Hepatol, doi:10.1016/S2468-1253(20)30048-0
Zaki, Van Boheemen, Bestebroer, Osterhaus, Fouchier, Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia, N Engl J Med, doi:10.1056/NEJMoa1211721
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Intensive Care Med, doi:10.1007/s00134-020-05985-9
Zhao, Zhao, Wang, Zhou, Ma et al., Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov, BioRxiv, doi:10.1101/2020.01.26.919985
Zhou, Vedantham, Lu, Agudelo, Carrion et al., Protease inhibitors targeting coronavirus and filovirus entry, Antiviral Res, doi:10.1016/j.antiviral.2015.01.011
Zhu, Zhang, Li, Yang, Song, A Novel Coronavirus from patients with pneumonia in China, 2019, N Engl J Med, doi:10.1056/NEJMoa2001017
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