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,
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'abstract': '<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Inhaled '
'budesonide benefits patients with COVID-19. <jats:italic>ProLung™-budesonide</jats:italic> '
'enables the sustained, low dose administration of budesonide within a delivery vehicle '
'similar to lung surfactant. <jats:italic>ProLung™-budesonide</jats:italic> may offer '
'anti-inflammatory and protective effects to the lung in COVID-19, yet it’s effect on '
'SARS-CoV-2 replication is '
'unknown.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To determine '
'the efficacy of <jats:italic>ProLung™-budesonide</jats:italic> against SARS-CoV-2 infection '
'in vitro, evaluate its ability to decrease inflammation, and airway hyperresponsiveness in an '
'animal model of lung '
'inflammation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>SARS-CoV-2-infected '
'Vero 76 cells were treated with <jats:italic>ProLung™-budesonide</jats:italic> ([0.03– 100 '
'μg/ml]) for 3 days, and virus yield in the supernatant was measured. 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 > 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. '
'This novel drug formulation may offer a potential inhalational treatment for '
'COVID-19.</jats:p></jats:sec>',
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