Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation.

Background: Inhaled budesonide benefits patients with COVID-19. enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant. 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 against SARS-CoV-2-infection , 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 ([0.03-100 µg/ml]) for 3 days, and virus yield in the supernatant was measured. Ovalbumin-sensitized C57BL/6 mice received aerosolized (a) weekly, (b) only budesonide, either daily or weekly, or (c) weekly empty (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: showed significant inhibition of viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value >24. Weekly and daily budesonide therapy significantly decreased lung inflammation and EPO in BAL. localized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challenge.

Conclusions: 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.