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ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation

Konduri et al., bioRxiv, doi:10.1101/2021.05.05.442779
May 2021  
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Budesonide for COVID-19
19th treatment shown to reduce risk in April 2021, now with p = 0.0000011 from 15 studies, recognized in 8 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
In Vitro study and animal study showing that ProLung™-budesonide inhibits SARS-CoV-2 replication (results for budesonide were not provided). ProLung™-budesonide and budesonide significantly decreased lung inflammation. ProLung™-budesonide is a formulation for sustained administration of a low dose of budesonide using a vehicle similar to lung surfactant.
3 preclinical studies support the efficacy of budesonide for COVID-19:
Konduri et al., 5 May 2021, preprint, 10 authors.
This PaperBudesonideAll
ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation
Kameswari S Konduri, Ram Pattisapu, Jogi Pattisapu, Girija G Konduri, John Zwetchkenbaum, Monalisa Barman ¥ Adria Frazier, Brett L Hurst
doi:10.1101/2021.05.05.442779
Background: Inhaled budesonide benefits patients with COVID-19. ProLung™-budesonide enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant. ProLung™-budesonide may offer anti-inflammatory and protective effects to the lung in COVID-19, yet it's effect on SARS-CoV-2 replication is unknown. Objective: To determine the efficacy of ProLung™-budesonide against SARS-CoV-2 infection in vitro, evaluate its ability to decrease inflammation, and airway hyperresponsiveness in an animal model of lung inflammation. Methods: SARS-CoV-2-infected Vero 76 cells were treated with ProLung™-budesonide ([0.03-100 µg/ml]) for 3 days, and virus yield in the supernatant was measured. Ovalbumin-sensitized C57BL/6 mice received aerosolized (a) ProLung™-budesonide weekly, (b) only budesonide, either daily or weekly, or (c) weekly empty ProLung™-carrier (without budesonide). All treatment groups were compared to sensitized untreated, or normal mice using histopathologic examination,
TABLES AND FIGURES
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Ovalbumin-sensitized ' 'C57BL/6 mice received aerosolized (a) <jats:italic>ProLung™-budesonide</jats:italic> weekly, ' '(b) only budesonide, either daily or weekly, or (c) weekly empty ' '<jats:italic>ProLung™-carrier</jats:italic> (without budesonide). All treatment groups were ' 'compared to sensitized untreated, or normal mice using histopathologic examination, electron ' 'microscopy (EM), airway hyperresponsiveness (AHR) to Methacholine (Mch) challenge, and ' 'eosinophil peroxidase activity (EPO) measurements in bronchioalveolar lavage ' '(BAL).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>ProLung™-budesonide</jats:italic> ' 'showed significant inhibition on viral replication of SARS-CoV-2-infected cells with the ' 'selectivity index (SI) value &gt; 24. Weekly <jats:italic>ProLung™-budesonide</jats:italic> ' 'and daily budesonide therapy significantly decreased lung inflammation and EPO in BAL. ' '<jats:italic>ProLung™-budesonide</jats:italic> localized in type II pneumocytes, and was the ' 'only group to significantly decrease AHR, and EPO in BAL with Mch ' 'challenge</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:italic>ProLung™-budesonide</jats:italic> ' 'significantly inhibited viral replication in SARS-CoV-2 infected cells. It localized into ' 'type II pneumocytes, decreased lung inflammation, AHR and EPO activity with Mch challenge. 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