Calu-3 is a cell line derived from a submucosal adenocarcinoma of the bronchi that grows in adherent culture and displays epithelial morphology.
Various studies have proposed the need to study SARS-CoV-2 infection in human respiratory epithelium to get closer to the central target tissue of the disease in patients ( 19). The Vero E6 cell line (African green monkey kidney) is deficient for type 1 interferons (IFNs) and highly susceptible to many different pathogens, like measles virus, rubella virus, arboviruses, adenoviruses, influenza, and some coronavirus, including SARS-CoV-2 ( 16– 18). It has recently been described that iota-carrageenan has activity against the SARS-CoV-2 virus and its Spike Pseudotyped Lentivirus (SSPL) in Vero E6 cell culture ( 14, 15). Based on these observations, the hypothesis has been raised that a nasal spray with iota-carrageenan could be effective against SARS-CoV-2. Iota-carrageenan formulated into a nasal spray has already been proven safe and effective in common cold treatment ( 13). It has also been shown that their inhibitory activity also relies on affecting the viral replication cycle at different steps, like entry and genome replication, and additionally activates the host's antiviral immune response ( 10– 12). Iota-carrageenan inhibits virus infection mainly based on its interaction with the surface of viral particles, preventing them from entering cells and trapping the viral particles released from the infected cells ( 9). Besides these properties, the iota-carrageenan demonstrated antiviral activity against several viruses, including respiratory viruses such as human rhinovirus, influenza A H1N1, and common cold coronavirus ( 6– 8). Marine-derived polysaccharides, such as carrageenans, are a family of linear sulfated polysaccharides extracted from red seaweeds, widely used as thickening agents and stabilizers for food. Repurposing established medications with recognized safety profiles is a possible approach for preventing or treating the disease and shortening the time-consuming drug development stages while the vaccination is being extended.ĭuring the first days of the infection, the virus replicates mainly in the nasal cavity and the nasopharynx therefore, nasal sprays with antiviral activity could prevent infection or, in case it occurs, could reduce the viral load in these zones ( 4, 5). Vaccines are the only tool that has been shown to be effective in preventing COVID-19 at the time of this publication, <40% of the world population has received a complete vaccination, and in developing countries, the percentage of individuals with complete vaccination is negligible, and only 3.1% of the population has received a single dose ( 3). There are, except for remdesivir, no approved antivirals for the treatment or prevention of SARS-CoV-2 infection. The severe acute respiratory coronavirus 2 (SARS-CoV-2) is responsible for the currently ongoing pandemic coronavirus disease (COVID-19), counting more than 243,857,028 confirmed cases and more than 4.953.246 deaths worldwide by Octo( 1, 2). In this study, the assayed formula, already approved as a nasal spray for human use, effectively inhibited SARS-CoV-2 infection, providing a more substantial reference for clinical studies or developments.
In Calu-3, a human respiratory epithelium cell line, we explored the activity of a formula of iota-carrageenan and sodium chloride against SARS-CoV-2. Iota-carrageenan is a sulfated polysaccharide extracted from red seaweeds, which, formulated into a nasal spray, has already been proven safe and effective in viral upper respiratory infections. César Milstein-(Consejo Nacional de Investigaciones Científicas y Técnicas CONICET-Fundación Pablo Cassará), Ciudad de Buenos Aires, Argentina 2Respiratory Research Group, Instituto de Ciencia y Tecnología Dr.1Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina.Augusto Varese 1 †, Ana Paletta 1 †, Ana Ceballos 1, Carlos Adolfo Palacios 2, Juan Manuel Figueroa 2 and Andrea Vanesa Dugour 2 *
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