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Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

Varese et al., bioRxiv, doi:10.1101/2021.04.27.441512

Apr 2021

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In Vitro Calu-3 (human respiratory epithelial cell line) study showing that iota-carrageenan inhibits SARS-CoV-2.

15 preclinical studies support the efficacy of iota-carrageenan for COVID-19:

4 In Silico studies1-4

11 In Vitro studies3,5-14

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1. Rohilla et al., Algae Polysaccharides (Carrageenan and Alginate)—A Treasure-Trove of Antiviral Compounds: An In Silico Approach to Identify Potential Candidates for Inhibition of S1-RBD Spike Protein of SARS-CoV-2, Stresses, doi:10.3390/stresses3030039.mdpi.com, doi.org.

2. Thet, H., The potential of carrageenan for the drug discovery of COVID-19 via molecular docking with angiotensin-converting enzyme 2 (ACE2) and the main protease (Mpro) of SARS-CoV-2, Journal of Bioinformatics and Genomics, doi:10.18454/jbg.2022.18.2.001.journal-biogen.org, doi.org.

3. Alsaidi et al., Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model, Marine Drugs, doi:10.3390/md19080418.mdpi.com, doi.org.

4. Sattari et al., Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors, Research Square, doi:10.21203/rs.3.rs-37994/v1.researchsquare.com, doi.org.

5. Yathindranath et al., Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection, International Journal of Nanomedicine, doi:10.2147/IJN.S448005.dovepress.com, doi.org.

6. Setz et al., Iota-Carrageenan Inhibits Replication of the SARS-CoV-2 Variants of Concern Omicron BA.1, BA.2 and BA.5, Nutraceuticals, doi:10.3390/nutraceuticals3030025.mdpi.com, doi.org.

7. Meister et al., Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2, Journal of Hospital Infection, doi:10.1016/j.jhin.2021.10.019.sciencedirect.com, doi.org.

8. Bovard et al., Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia, Biochemistry and Biophysics Reports, doi:10.1016/j.bbrep.2021.101187.sciencedirect.com, doi.org.

9. Fröba et al., Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta, International Journal of Molecular Sciences, doi:10.3390/ijms222413202.mdpi.com, doi.org.

10. Varese et al., Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model, bioRxiv, doi:10.1101/2021.04.27.441512.biorxiv.org, doi.org.

11. Morokutti-Kurz et al., Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro, PLoS ONE, doi:10.1371/journal.pone.0237480.plos.org, doi.org.

12. Song et al., Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2, Food & Function, doi:10.1039/D0FO02017F.rsc.org, doi.org.

13. Bansal et al., Iota-carrageenan and xylitol inhibit SARS-CoV-2 in Vero cell culture, PLoS ONE, doi:10.1371/journal.pone.0259943.plos.org, doi.org.

14. Morokutti-Kurz (B) et al., Amylmetacresol/2,4-dichlorobenzyl alcohol, hexylresorcinol, or carrageenan lozenges as active treatments for sore throat, International Journal of General Medicine, doi:10.2147/IJGM.S120665.dovepress.com, doi.org.

Varese et al., 27 Apr 2021, preprint, 5 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Iota-carragee..All

Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

Augusto Varese, Ana Ceballos, Carlos Palacios, Juan Manuel Figueroa, Andrea Vanesa Dugour

doi:10.1101/2021.04.27.441512

There are, except for remdesivir, no approved antivirals for the treatment or prevention of SARS-CoV-2 infections. Iota-carrageenan formulated into a nasal spray has already been proven safe and effective in viral respiratory infections. We explored this antiviral activity in Calu-3, a human respiratory model cell line. A formula of iota-carrageenan and sodium chloride, as a nasal spray, already approved for human use, effectively inhibited SARS-CoV-2 infection in vitro, providing a more substantial reference for further clinical studies or developments.

Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions AC, AVD, and JMF conceptualized the study. AC, AV, CP and AVD developed the methodology. JMF wrote and prepared the original draft. AC, AVD, and CP wrote, reviewed, and edited the manuscript. AC and AVD supervised the study. All authors contributed to the article and approved the submitted version.

References

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Bansal, Jonsson, Taylor, Figueroa, Dugour et al., Iota-carrageenan and Xylitol inhibit SARS-CoV-2 in cell culture, Biorxiv, doi:10.1101/2020.08.19.225854

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Morokutti-Kurz, König-Schuster, Koller, Graf, Graf et al., The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model, Plos One, doi:10.1371/journal.pone.0128794

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