Advanced in vitro exposure systems.

Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia

9. Dec. 2021

https://doi.org/10.1016/j.bbrep.2021.101187

David Bovard b, Marco van der Toorn b, Walter K. Schlage a, Samuel Constant c, Kasper Renggli b, Manuel C. Peitsch b, Julia Hoeng b,
a Biology Consultant, Max-Baermann-Str. 21, 51429, Bergisch Gladbach, Germany
b PMI R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
c Epithelix Sarl, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland

 

This study successfully demonstrates the exposure of human bronchial epithelial cultures to defined doses of nebulized Iota-carrageenan which were reproducibly generated and administered using the VITROCELL Cloud 12 system. 
The aim of this study was to further investigate the efficacy and safety of IC treatment on SARS-CoV-2 infection by using advanced in vitro models of human respiratory epithelium, the primary target and entry port of SARS-CoV-2. The experimental models were 3D cultures of reconstituted bronchial and nasal epithelia, representing the surface of the human upper respiratory tract. This apical exposure of reconstructed epithelia more closely mimics real-life exposure conditions and the absence of toxicity or any functional or structural impairment of the bronchial mucociliary epithelium demonstrates that topical treatment with nebulized IC is well tolerated at the effective concentrations. 

 

Abstract

Iota-carrageenan (IC) nasal spray, a medical device approved for treating respiratory viral infections, has pre- viously been shown to inhibit the ability of a variety of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to enter and replicate in the cell by interfering with the virus binding to the cell surface. The aim of this study was to further investigate the efficacy and safety of IC in SARS-CoV-2 infection in advanced in vitro models of the human respiratory epithelium, the primary target and entry port for SARS-CoV-2. We extended the in vitro safety assessment of nebulized IC in a 3-dimensional model of reconstituted human bronchial epithelium, and we demonstrated the efficacy of IC in protecting reconstituted nasal epithelium against viral infection and replication of a patient-derived SARS-CoV-2 strain. The results ob- tained from these two advanced models of human respiratory tract epithelia confirm previous findings from in vitro SARS-CoV-2 infection assays and demonstrate that topically applied IC can effectively prevent SARS-CoV-2 infection and replication. Moreover, the absence of toxicity and functional and structural impairment of the mucociliary epithelium demonstrates that the nebulized IC is well tolerated.

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