Antiviral Effect of Budesonide against SARS-CoV-2
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.
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