ProLung™-budesonideInhibits SARS-CoV-2 Replication and Reduces Lung Inflammation

  1. Kameswari S. Konduri
  2. Ram Pattisapu
  3. Jogi Pattisapu
  4. Girija G. Konduri
  5. John Zwetchkenbaum
  6. Bidhan Roy
  7. Monalisa Barman
  8. Adria Frazier
  9. Brett L. Hurst
  10. Nejat Düzgüneş
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Abstract

Background

Inhaled budesonide benefits patients with COVID-19.ProLung™-budesonideenables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant.ProLung™-budesonidemay 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 ofProLung™-budesonideagainst 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 withProLung™-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™-budesonideweekly, (b) only budesonide, either daily or weekly, or (c) weekly emptyProLung™-carrier(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).

Results

ProLung™-budesonideshowed significant inhibition on viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value > 24. WeeklyProLung™-budesonideand daily budesonide therapy significantly decreased lung inflammation and EPO in BAL.ProLung™-budesonidelocalized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challenge

Conclusions

ProLung™-budesonidesignificantly 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.

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