Antiviral Effect of Budesonide against SARS-CoV-2
Natalie Heinen, Toni Luise Meister, Mara Klöhn, Eike Steinmann, Daniel Todt, Stephanie Pfaender
Viruses, doi:10.3390/v13071411
Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of treatment for COVID-19, partly based on a previous study that reported reduced recovery times in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. Given various reports that describe the potential antiviral activity of glucocorticoids against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between all viral variants tested while cell viability remains unaffected. Our results are encouraging as they could indicate a multimodal mode of action of budesonide against SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance.
Author Contributions: S.P. designed the project; N.H. and T.L.M. performed the experiments; N.H., S.P. and M.K. wrote the manuscript; D.T. evaluated the data; E.S. and S.P. supervised the study. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
Data Availability Statement: The data generated and analyzed in this study are included in the article. Viruses 2021, 13, 1411 Conflicts of Interest: The authors declare no conflict of interest.
References
Arabi, Mandourah, Al-Hameed, Sindi, Almekhlafi et al., Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome, Am. J. Respir. Crit. Care Med,
doi:10.1164/rccm.201706-1172OC
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the Treatment of Covid-19-Final Report, N. Engl. J. Med,
doi:10.1056/NEJMoa2007764
Chen, Li, Influence of Corticosteroid Dose on Viral Shedding Duration in Patients With COVID-19, Clin. Infect. Dis,
doi:10.1093/cid/ciaa832
Davies, Carroll, Li, Poh, Kirkegard et al., Budesonide and formoterol reduce early innate anti-viral immune responses in vitro, PLoS ONE,
doi:10.1371/journal.pone.0027898
Deliloglu, Tuzun, Cengiz, Ozkan, Duman, Endotracheal Surfactant Combined With Budesonide for Neonatal ARDS, Front. Pediatr,
doi:10.3389/fped.2020.00210
Ding, Feng, Chen, Yuan, Yi et al., Effect of Corticosteroid Therapy on the Duration of SARS-CoV-2 Clearance in Patients with Mild COVID-19: A Retrospective Cohort Study, Infect. Dis. Ther,
doi:10.1007/s40121-020-00337-y
Gibson, Saltos, Fakes, Acute anti-inflammatory effects of inhaled budesonide in asthma: A randomized controlled trial, Am. J. Respir. Crit. Care Med,
doi:10.1164/ajrccm.163.1.9807061
Halpin, Faner, Sibila, Badia, Agusti, Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?, Lancet Respir. Med,
doi:10.1016/S2213-2600(20)30167-3
Horby, Lim, Emberson, Mafham, Bell et al., Dexamethasone in Hospitalized Patients with Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2021436
Kim, Song, Ahn, Lee, Ahn et al., Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation, Antiviral Res,
doi:10.1016/j.antiviral.2018.01.012
Li, Hu, Song, High-dose but Not Low-dose Corticosteroids Potentially Delay Viral Shedding of Patients With COVID-19, Clin. Infect. Dis,
doi:10.1093/cid/ciaa829
Matsuyama, Kawase, Nao, Shirato, Ujike et al., The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells, J. Virol,
doi:10.1128/JVI.01648-20
Mendes, Rebolledo, Campos, Wanner, Immediate antiinflammatory effects of inhaled budesonide in patients with asthma, Ann. Am. Thorac. Soc,
doi:10.1513/AnnalsATS.201307-220OC
Mohamed, Meguid, Effect of nebulized budesonide on respiratory mechanics and oxygenation in acute lung injury/acute respiratory distress syndrome: Randomized controlled study, Saudi J. Anaesth,
doi:10.4103/1658-354X.197369
Ramakrishnan, Nicolau, Langford, Mahdi, Jeffers et al., Inhaled budesonide in the treatment of early COVID-19 (STOIC): A phase 2, open-label, randomised controlled trial, Lancet Respir. Med,
doi:10.1016/S2213-2600(21)00160-0
Sterne, Murthy, Diaz, Slutsky, Villar et al., Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis, JAMA,
doi:10.1001/jama.2020.17023
Szafranski, Cukier, Ramirez, Menga, Sansores et al., Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease, Eur. Respir. J,
doi:10.1183/09031936.03.00031402
Wang, Zhang, Du, Du, Zhao et al., Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial, Lancet,
doi:10.1016/S0140-6736(20)31022-9
Yamaya, Nishimura, Deng, Sugawara, Watanabe et al., Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells, Respir. Investig,
doi:10.1016/j.resinv.2019.12.005
Zetterström, Buhl, Mellem, Perpiñá, Hedman et al., Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone, Eur. Respir. J,
doi:10.1183/09031936.01.00065801
Zhou, Dejnirattisai, Supasa, Liu, Mentzer et al., Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera, Cell
Zhu, Zhang, Wang, Li, Yang et al., A Novel Coronavirus from Patients with Pneumonia in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2001017
{ 'indexed': {'date-parts': [[2024, 5, 6]], 'date-time': '2024-05-06T22:35:51Z', 'timestamp': 1715034951723},
'reference-count': 30,
'publisher': 'MDPI AG',
'issue': '7',
'license': [ { 'start': { 'date-parts': [[2021, 7, 20]],
'date-time': '2021-07-20T00:00:00Z',
'timestamp': 1626739200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>Treatment options for COVID-19, a disease caused by Severe\xa0Acute\xa0Respiratory\xa0'
'Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, '
'antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms '
'are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of '
'treatment for COVID-19, partly based on a previous study that reported reduced recovery times '
'in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. '
'Given various reports that describe the potential antiviral activity of glucocorticoids '
'against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide '
'against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 '
'(beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between '
'all viral variants tested while cell viability remains unaffected. Our results are '
'encouraging as they could indicate a multimodal mode of action of budesonide against '
'SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance.</jats:p>',
'DOI': '10.3390/v13071411',
'type': 'journal-article',
'created': {'date-parts': [[2021, 7, 20]], 'date-time': '2021-07-20T15:26:10Z', 'timestamp': 1626794770000},
'page': '1411',
'source': 'Crossref',
'is-referenced-by-count': 14,
'title': 'Antiviral Effect of Budesonide against SARS-CoV-2',
'prefix': '10.3390',
'volume': '13',
'author': [ { 'ORCID': 'http://orcid.org/0000-0003-0906-5073',
'authenticated-orcid': False,
'given': 'Natalie',
'family': 'Heinen',
'sequence': 'first',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-8962-9443',
'authenticated-orcid': False,
'given': 'Toni Luise',
'family': 'Meister',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-7707-2040',
'authenticated-orcid': False,
'given': 'Mara',
'family': 'Klöhn',
'sequence': 'additional',
'affiliation': []},
{'given': 'Eike', 'family': 'Steinmann', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-3564-1014',
'authenticated-orcid': False,
'given': 'Daniel',
'family': 'Todt',
'sequence': 'additional',
'affiliation': []},
{'given': 'Stephanie', 'family': 'Pfaender', 'sequence': 'additional', 'affiliation': []}],
'member': '1968',
'published-online': {'date-parts': [[2021, 7, 20]]},
'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001017'},
{'key': 'ref2'},
{'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)31022-9'},
{'key': 'ref4'},
{'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2007764'},
{'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cell.2021.02.037'},
{ 'key': 'ref7',
'unstructured': 'COG-UK report on SARS-CoV-2 Spike mutations of interestin the UK\n'
'https://www.cogconsortium.uk/wp-content/uploads/2021/01/Report-2_COG-UK_SARS-CoV-2-Mutations.pdf'},
{'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2213-2600(21)00160-0'},
{'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2213-2600(20)30167-3'},
{'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.1183/09031936.01.00065801'},
{ 'key': 'ref11',
'unstructured': 'Global Strategy for Asthma Management and Prevention\n'
'https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf'},
{'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.1183/09031936.03.00031402'},
{'key': 'ref13', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2018.01.012'},
{'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/JVI.01648-20'},
{'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.resinv.2019.12.005'},
{ 'key': 'ref16',
'unstructured': 'Therapeutics and COVID-19\n'
'https://apps.who.int/iris/bitstream/handle/10665/336729/WHO-2019-nCov-remdesivir-2020.1-eng.pdf'},
{'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40121-020-00337-y'},
{'key': 'ref18', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciaa832'},
{'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.1164/rccm.201706-1172OC'},
{'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciaa829'},
{'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.17023'},
{'key': 'ref22', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2021436'},
{'key': 'ref23'},
{'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.1183/13993003.02049-2020'},
{'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fped.2020.00210'},
{'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.4103/1658-354X.197369'},
{'key': 'ref27', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0027898'},
{'key': 'ref28', 'doi-asserted-by': 'publisher', 'DOI': '10.1164/ajrccm.163.1.9807061'},
{'key': 'ref29', 'doi-asserted-by': 'publisher', 'DOI': '10.1164/ajrccm.162.3.9910077'},
{'key': 'ref30', 'doi-asserted-by': 'publisher', 'DOI': '10.1513/AnnalsATS.201307-220OC'}],
'container-title': 'Viruses',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/1999-4915/13/7/1411/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 7, 20]],
'date-time': '2021-07-20T17:18:23Z',
'timestamp': 1626801503000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/1999-4915/13/7/1411'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 7, 20]]},
'references-count': 30,
'journal-issue': {'issue': '7', 'published-online': {'date-parts': [[2021, 7]]}},
'alternative-id': ['v13071411'],
'URL': 'http://dx.doi.org/10.3390/v13071411',
'relation': {},
'ISSN': ['1999-4915'],
'subject': [],
'container-title-short': 'Viruses',
'published': {'date-parts': [[2021, 7, 20]]}}