nach oben

Internal and Emergency Medicine

Erschienen in:

26.05.2020 | COVID-19 | IM - REVIEW Zur Zeit gratis

Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?

verfasst von: Markus Depfenhart, Danielle de Villiers, Gottfried Lemperle, Markus Meyer, Salvatore Di Somma

Erschienen in: Internal and Emergency Medicine | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

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.

World Health Organization (2020) Coronavirus disease (COVID-2019) press briefings. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/press-briefings. Accessed 22 Mar 2020

World Health Organization (2020) Coronavirus Disease (COVID-2019) Situation Reports 1–89. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed 18 Apr 2020

Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker S et al (2003) Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348(20):1967–1976. https://doi.org/10.1056/NEJMoa030747(Epub 2003/04/12, PubMed PMID: 12690091)CrossRefPubMed

Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S et al (2003) A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348(20):1953–1966. https://doi.org/10.1056/NEJMoa030781(Epub 2003/04/12, PubMed PMID: 12690092)CrossRefPubMed

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367(19):1814–1820. https://doi.org/10.1056/NEJMoa1211721(Epub 2012/10/19, PubMed PMID: 2307514)CrossRefPubMed

Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA et al (2020) The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. https://doi.org/10.1038/s41564-020-0695-zCrossRef

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al (2020) A Novel Coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382(8):727–733. https://doi.org/10.1056/NEJMoa2001017(Epub 2020/01/25, PubMed PMID: 31978945)CrossRefPubMedPubMedCentral

Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R (2020) Features, evaluation and treatment coronavirus (COVID-19). StatPearls Publishing, St. Petersburg

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG et al (2020) A new coronavirus associated with human respiratory disease in China. Nature 579(7798):265–269. https://doi.org/10.1038/s41586-020-2008-3(Epub 2020/02/06, PubMed PMID: 32015508)CrossRefPubMedPubMedCentral

10.

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S et al (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 9(1):221–236. https://doi.org/10.1080/22221751.2020.1719902(Epub 2020/01/29, PubMed PMID: 31987001)CrossRefPubMedPubMedCentral

11.

Li G, De Clercq E (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 19(3):149–150. https://doi.org/10.1038/d41573-020-00016-0(Epub 2020/03/05, PubMed PMID: 32127666)CrossRefPubMed

12.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY) 367(6483):1260–1263. https://doi.org/10.1126/science.abb2507(Epub 2020/02/23, PubMed PMID: 32075877)CrossRef

13.

Kirchdoerfer RN, Cottrell CA, Wang N, Pallesen J, Yassine HM, Turner HL et al (2016) Pre-fusion structure of a human coronavirus spike protein. Nature 531(7592):118–121. https://doi.org/10.1038/nature17200(Epub 2016/03/05, PubMed PMID: 26935699; PubMed Central PMCID: PMCPMC4860016)CrossRefPubMedPubMedCentral

14.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England) 395(10224):565–574. https://doi.org/10.1016/S0140-6736(20)30251-8(PubMed PMID: 32007145)CrossRef

15.

Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. https://doi.org/10.1128/jvi.00127-20(Epub 2020/01/31, PubMed PMID: 31996437)CrossRefPubMedPubMedCentral

16.

Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W (2020) Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv. https://doi.org/10.1101/2020.01.26.919985CrossRefPubMedPubMedCentral

17.

Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE et al (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417(6891):822–828. https://doi.org/10.1038/nature00786CrossRefPubMed

18.

Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y et al (2005) Multiple organ infection and the pathogenesis of SARS. J Exp Med 202(3):415–424. https://doi.org/10.1084/jem.20050828(Epub 2005/07/27)CrossRefPubMedPubMedCentral

19.

Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M et al (2012) ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487(7408):477–481. https://doi.org/10.1038/nature11228(Epub 2012/07/28)CrossRefPubMedPubMedCentral

20.

Yeo C, Kaushal S, Yeo D (2020) Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol 5(4):335–337. https://doi.org/10.1016/S2468-1253(20)30048-0CrossRefPubMedPubMedCentral

21.

Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307(23):2526–2533. https://doi.org/10.1001/jama.2012.5669(Epub 2012/07/17)CrossRefPubMed

22.

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L et al (2020) COVID-19 pneumonia: different respiratory treatment for different phenotypes? Intensive Care Med. https://doi.org/10.1007/s00134-020-06033-2CrossRefPubMedPubMedCentral

23.

Craven J (2020) Covid-19 vaccine tracker. Regulatory affairs professionals society. https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker. Accessed 30 Mar 2020

24.

Simmons G, Zmora P, Gierer S, Heurich A, Pöhlmann S (2013) Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res 100(3):605–614. https://doi.org/10.1016/j.antiviral.2013.09.028CrossRefPubMedPubMedCentral

25.

Belouzard S, Millet JK, Licitra BN, Whittaker GR (2012) Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4(6):1011–1033. https://doi.org/10.3390/v4061011(Epub 2012/07/21)CrossRefPubMedPubMedCentral

26.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. https://doi.org/10.1016/j.cell.2020.02.052(Epub 2020/03/07)CrossRefPubMedPubMedCentral

27.

Drugs. Camostat. 2020. https://www.drugs.com/international/camostat.html. Accessed 22 Mar 2020

28.

Ramsey ML, Nuttall J, Hart PA, 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 20(1):501. https://doi.org/10.1186/s13063-019-3606-yCrossRefPubMedPubMedCentral

29.

Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R, Nunneley JW et al (2015) Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 116:76–84. https://doi.org/10.1016/j.antiviral.2015.01.011CrossRefPubMedPubMedCentral

30.

Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue J-I et al (2016) 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 60(11):6532–6539. https://doi.org/10.1128/AAC.01043-16(PubMed PMID: 27550352)CrossRefPubMedPubMedCentral

31.

Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD et al (2014) The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov 4(11):1310–1325. https://doi.org/10.1158/2159-8290.cd-13-1010(Epub 2014/08/15)CrossRefPubMedPubMedCentral

32.

Chang CC, Cheng AC, Chang AB (2007) Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children and adults. Cochrane Database Syst Rev 4:Cd006088. https://doi.org/10.1002/14651858.CD006088.pub2(Epub 2007/10/19)CrossRef

33.

Danelius E, Andersson H, Jarvoll P, Lood K, Gräfenstein J, Erdélyi M (2017) Halogen bonding: a powerful tool for modulation of peptide conformation. Biochemistry 56(25):3265–3272. https://doi.org/10.1021/acs.biochem.7b00429(PubMed PMID: 28581720)CrossRefPubMed

34.

Mikkonen L, Pihlajamaa P, Sahu B, Zhang FP, Janne OA (2010) Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol 317(1–2):14–24. https://doi.org/10.1016/j.mce.2009.12.022(Epub 2009/12/29)CrossRefPubMed

35.

Drugs (2020) Antiandrogens. https://www.drugs.com/drug-class/antiandrogens.html. Accessed 14 Apr 2020

36.

Sanofi-Synthelabo Inc. (2001) Chloroquine FDA label. https://s3-us-west-2.amazonaws.com/drugbank/fda_labels/DB00608.pdf?1265922797. Accessed 22 Mar 2020

37.

Aguiar ACC, Murce E, Cortopassi WA, Pimentel AS, Almeida M, Barros DCS et al (2018) Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity. Int J Parasitol Drugs Drug Resist 8(3):459–464. https://doi.org/10.1016/j.ijpddr.2018.10.002(Epub 2018/11/06)CrossRefPubMedPubMedCentral

38.

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG et al (2005) Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2(1):69. https://doi.org/10.1186/1743-422X-2-69CrossRefPubMedPubMedCentral

39.

Jang CH, Choi JH, Byun MS, Jue DM (2006) Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford, England) 45(6):703–710. https://doi.org/10.1093/rheumatology/kei282(Epub 2006/01/19)CrossRef

40.

Golden E, Cho H-Y, Hofman F, Louie S, Schonthal A, Chen T (2015) Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus 38:E12. https://doi.org/10.3171/2014.12.FOCUS14748CrossRefPubMed

41.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M et al (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3):269–271. https://doi.org/10.1038/s41422-020-0282-0CrossRefPubMedPubMedCentral

42.

Gautret P, Lagier JC, Parola P, Hoang VT, Medded L, Mailhe M et al (2020) Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial. medRxiv. https://doi.org/10.1101/2020.03.16.20037135CrossRef

43.

Weniger H (1979) Review of side effects and toxicity of chloroquine. World Health Organization, Geneva

44.

McChesney EW (1983) Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med 75(1a):11–18. https://doi.org/10.1016/0002-9343(83)91265-2(Epub 1983/07/18)CrossRefPubMed

45.

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS (2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. https://doi.org/10.1007/s00134-020-05985-9CrossRefPubMedPubMedCentral

46.

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H et al (2020) Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 6(1):16. https://doi.org/10.1038/s41421-020-0156-0CrossRefPubMedPubMedCentral

47.

Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B et al (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11(8):875–879. https://doi.org/10.1038/nm1267(Epub 2005/07/12)CrossRefPubMedPubMedCentral

48.

Rubio-Aliaga I, Frey I, Boll M, Groneberg DA, Eichinger HM, Balling R et al (2003) Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney. Mol Cell Biol 23(9):3247–3252CrossRefPubMedPubMedCentral

49.

Ding N, Zhao K, Lan Y, Li Z, Lv X, Su J et al (2017) Induction of atypical autophagy by porcine hemagglutinating encephalomyelitis virus contributes to viral replication. Front Cell Infect Microbiol 7:56. https://doi.org/10.3389/fcimb.2017.00056(Epub 2017/03/16)CrossRefPubMedPubMedCentral

50.

Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B et al (2012) Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochem Biophys Acta 1824(1):68–88. https://doi.org/10.1016/j.bbapap.2011.10.002(Epub 2011/10/26)CrossRefPubMed

51.

Frlan R, Gobec S (2006) Inhibitors of cathepsin B. Curr Med Chem 13:2309–2327. https://doi.org/10.2174/092986706777935122CrossRefPubMed

52.

Schrezenmeier E, Dorner T (2020) Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 16(3):155–166. https://doi.org/10.1038/s41584-020-0372-x(Epub 2020/02/09)CrossRefPubMed

53.

Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X et al (2018) Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 9(2):e00221–e318. https://doi.org/10.1128/mBio.00221-18CrossRefPubMedPubMedCentral

54.

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H et al (2020) First case of 2019 novel coronavirus in the United States. N Engl J Med 382(10):929–936. https://doi.org/10.1056/NEJMoa2001191(PubMed PMID: 32004427)CrossRefPubMedPubMedCentral

55.

Fehr AR, Perlman S (2015) Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol (Clifton, NJ) 1282:1–23. https://doi.org/10.1007/978-1-4939-2438-7_1(Epub 2015/02/28)CrossRef

56.

Harcourt BH, Jukneliene D, Kanjanahaluethai A, Bechill J, Severson KM, Smith CM et al (2004) Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. J Virol 78(24):13600–13612. https://doi.org/10.1128/jvi.78.24.13600-13612.2004(Epub 2004/11/27)CrossRefPubMedPubMedCentral

57.

Báez-Santos YM, St John SE, Mesecar AD (2015) The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res 115:21–38. https://doi.org/10.1016/j.antiviral.2014.12.015(Epub 12/29)CrossRefPubMed

58.

Chen YW, Yiu C-PB, Wong K-Y (2020) 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 9:129. https://doi.org/10.1288/f1000research.22457.1CrossRefPubMedPubMedCentral

59.

Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ et al (2020) 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 35(6):e79. https://doi.org/10.3346/jkms.2020.35.e79(Epub 2020/02/15)CrossRefPubMedPubMedCentral

60.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G et al (2020) A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. https://doi.org/10.1056/NEJMoa2001282CrossRefPubMedPubMedCentral

61.

Huynh T, Wang H, Luan B (2020) In silico exploration of the molecular mechanism of clinically oriented drugs for possibly inhibiting SARS-CoV-2’s main protease. J Phys Chem Lett11:4413–4420. https://doi.org/10.1021/acs.jpclett.0c00994CrossRefPubMedPubMedCentral

62.

Gulati K, Rai N, Chaudhary S, Ray A (2016) Nutraceuticals in respiratory disorders. Academic Press, Cambridge, pp 75–86

63.

Han S, Mallampalli RK (2015) The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc 12(5):765–774. https://doi.org/10.1513/AnnalsATS.201411-507FRCrossRefPubMedPubMedCentral

64.

Plomer M, de Zeeuw J (2017) More than expectorant: new scientific data on ambroxol in the context of the treatment of bronchopulmonary diseases. MMW Fortschritte der Medizin 159(Suppl 5):22–33. https://doi.org/10.1007/s15006-017-9805-0(Epub 2017/06/24)CrossRefPubMed

65.

Gao X, Huang Y, Han Y, Bai C-X, Wang G (2011) The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats. Arch Med Sci 7(3):405–413. https://doi.org/10.5114/aoms.2011.23403(Epub 07/11)CrossRefPubMedPubMedCentral

66.

Boehringer Ingelheim Limited (2016) Summary of bisolvon product characteristics. https://www.hpra.ie/img/uploaded/swedocuments/LicenseSPC_PA0007-025-002_29042016142022.pdf. Accessed 20 Mar 2020

67.

Therapeutic Goods Administration (TGA) (2012) Bisolvon chesty product information. https://gp2u.com.au/static/pdf/B/BISOLVON_CHESTY-PI.pdf. Accessed 21 Mar 2020.

68.

Laporte M, Naesens L (2017) Airway proteases: an emerging drug target for influenza and other respiratory virus infections. Curr Opin Virol 24:16–24. https://doi.org/10.1016/j.coviro.2017.03.018(Epub 2017/04/18)CrossRefPubMedPubMedCentral

69.

Waldrop T, Alsup D, McLaughlin EC (2020) Fearing coronavirus, Arizona man dies after taking a form of chloroquine used to treat aquariums. CNN Health. https://edition.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html. Accessed 30 Mar 2020.

70.

Touret F, de Lamballerie X (2020) Of chloroquine and COVID-19. Antiviral Res 177:104762. https://doi.org/10.1016/j.antiviral.2020.104762CrossRefPubMedPubMedCentral

71.

Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M et al (2009) Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother 53(8):3416–3421. https://doi.org/10.1128/aac.01509-08CrossRefPubMedPubMedCentral

72.

Tan YW, Yam WK, Sun J, Chu JJH (2018) An evaluation of chloroquine as a broad-acting antiviral against hand, foot and mouth disease. Antiviral Res 149:143–149. https://doi.org/10.1016/j.antiviral.2017.11.017(Epub 2017/11/28)CrossRefPubMed

73.

Yan Y, Zou Z, Sun Y, Li X, Xu K-F, Wei Y et al (2013) Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res 23(2):300–302. https://doi.org/10.1038/cr.2012.165CrossRefPubMed

74.

Paton NI, Lee L, Xu Y, Ooi EE, Cheung YB, Archuleta S et al (2011) Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. Lancet Infect Dis 11(9):677–683. https://doi.org/10.1016/S1473-3099(11)70065-2CrossRefPubMed

75.

Shimizu Y, Yamamoto S, Homma M, Ishida N (1972) Effect of chloroquine on the growth of animal viruses. Archiv für die gesamte Virusforschung 36(1):93–104. https://doi.org/10.1007/BF01250299CrossRefPubMed

76.

Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M (2004) In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun 323(1):264–268. https://doi.org/10.1016/j.bbrc.2004.08.085(Epub 2004/09/08)CrossRefPubMedPubMedCentral

77.

Inglot AD (1969) Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J Gen Virol 4(2):203–214. https://doi.org/10.1099/0022-1317-4-2-203CrossRefPubMed

78.

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D (2020) 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. https://doi.org/10.1093/cid/ciaa237CrossRefPubMedPubMedCentral

79.

Good MI, Shader RI (1982) Lethality and behavioral side effects of chloroquine. J Clin Psychopharmacol 2(1):40–47. https://doi.org/10.1097/00004714-198202000-00005(Epub 1982/02/01)CrossRefPubMed

80.

Bottcher-Friebertshauser E, Lu Y, Meyer D, Sielaff F, Steinmetzer T, Klenk HD et al (2012) Hemagglutinin activating host cell proteases provide promising drug targets for the treatment of influenza A and B virus infections. Vaccine 30(51):7374–7380. https://doi.org/10.1016/j.vaccine.2012.10.001(Epub 2012/10/18)CrossRefPubMed

Titel: Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
verfasst von: Markus Depfenhart
Danielle de Villiers
Gottfried Lemperle
Markus Meyer
Salvatore Di Somma
Publikationsdatum: 26.05.2020
Verlag: Springer International Publishing
Schlagwort: COVID-19
Erschienen in: Internal and Emergency Medicine / Ausgabe 5/2020
Print ISSN: 1828-0447
Elektronische ISSN: 1970-9366
DOI: https://doi.org/10.1007/s11739-020-02383-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2020

Managing anticoagulation in the COVID-19 era between lockdown and reopening phases

Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients

Providing evidence on the ongoing health care workers’ mask debate

Potential role of incretins in diabetes and COVID-19 infection: a hypothesis worth exploring

The burden of thrombotic complications in critically ill patients with COVID-19: charting the uncharted

Does this patient have COVID-19? A practical guide for the internist

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin