Development of an inhalable antiviral powder formulation against respiratory syncytial virus.

Respiratory viruses including the respiratory syncytial virus (RSV) aggravate the global burden of virus-inflicted morbidity and mortality. Entry inhibitors are a promising class of antiviral drugs for combating these viruses, as they can prevent infection at the site of viral entry, i.e., the respiratory tract. Here we used a broad-spectrum entry inhibitor, composed of a β-cyclodextrin backbone, functionalized with 11-mercapto-1-undecanesulfonate (CD-MUS) that is capable of neutralizing a variety of viruses that employ heparan sulfate proteoglycans (HSPG) to infect host cells. CD-MUS inactivates viral particles irreversibly by binding to viral attachment proteins through a multivalent binding mechanism. In the present study, we show that CD-MUS is well tolerated when administered to the respiratory tract of mice. Based on this, we developed an inhalable spray-dried powder formulation that fits the size requirements for lung deposition and disperses well upon use with the Cyclops dry powder inhaler (DPI). Using an in vitro dose-response assay, we show that the compound retained its activity against RSV after the spray drying process. Our study sets the stage for further in vivo studies, exploring the efficacy of pulmonary administered CD-MUS in animal models of RSV infection.

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Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Francesco Stellacci is inventor on patent number WO 2018/015465 A1 - Virucidal compounds and uses thereof. Francesco Stellacci and Paulo H. Jacob Silva are co-founders of Asterivir, a start-up company that focuses on developing novel antivirals. The employer of Henderik W. Frijlink holds a license agreement with PureIMS on the Twincer and Cyclops dry powder inhalers. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; nor in the writing of the manuscript or in the decision to submit the article for publication.