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

Abstract

BackgroundInhaled 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.ObjectiveTo 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.MethodsSARS-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, electron microscopy (EM), airway hyperresponsiveness (AHR) to Methacholine (Mch) challenge, and eosinophil peroxidase activity (EPO) measurements in bronchioalveolar lavage (BAL).ResultsProLung™-budesonide showed significant inhibition on viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value > 24. Weekly ProLung™-budesonide and daily budesonide therapy significantly decreased lung inflammation and EPO in BAL. ProLung™-budesonide localized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challengeConclusionsProLung™-budesonide 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.

Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design

“…Many viral infections are transmitted via the respiratory route, including SARS-CoV-2 and the influenza virus. Thus, the delivery by inhalation of free peptides or peptides anchored in liposomal membranes may be an efficient method to reach sites of initial infection [187].…”