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

David Bovard; Marco van der Toorn; Walter K Schlage; Samuel Constant; Kasper Renggli; Manuel C Peitsch; Julia Hoeng

doi:10.1016/j.bbrep.2021.101187

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

Biochem Biophys Rep. 2022 Mar:29:101187. doi: 10.1016/j.bbrep.2021.101187. Epub 2021 Dec 15.

Authors

David Bovard¹, Marco van der Toorn¹, Walter K Schlage², Samuel Constant³, Kasper Renggli¹, Manuel C Peitsch¹, Julia Hoeng¹

Affiliations

¹ PMI R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.
² Biology Consultant, Max-Baermann-Str. 21, 51429, Bergisch Gladbach, Germany.
³ Epithelix Sarl, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland.

Abstract

Iota-carrageenan (IC) nasal spray, a medical device approved for treating respiratory viral infections, has previously 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 obtained 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.

Keywords: 3D, 3-dimensional; AE, after exposure; ALI, air–liquid interface; Air–liquid interface; BE, before exposure; Bronchial epithelium; CBF, ciliary beating frequency; COVID-19; COVID19, Coronavirus disease 2019; DMMB, Dimethylmethylene blue; IC, Iota-carrageenan; Iota-carrageenan; LDH, lactate dehydrogenase; MOI, multiplicity of infection; NHBE, normal human bronchial epithelial; Nasal epithelium; Nasal spray; PBS, phosphate-buffered saline; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SSPL, spike-pseudotyped lentivirus; TEER, transepithelial electrical resistance; hACE2, human angiotensin I-converting enzyme 2.