Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro

Morokutti-Kurz et al., PLoS ONE, doi:10.1371/journal.pone.0237480

Feb 2021

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In Vitro study showing that SARS-CoV-2 is inhibited by iota-carrageenan in a dose dependent manner and to the same extent as other respiratory viruses for which a clinical benefit has been proven. Authors note that clinical data and post market surveillance data show that iota-carrageenan is well-tolerated with very low reported adverse events.

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.

Morokutti-Kurz et al., 17 Feb 2021, peer-reviewed, 8 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 neutralizes SARS-CoV-2 and inhibits viral replication in vitro

Martina Morokutti-Kurz, Maria Fröba, Philipp Graf, Maximilian Große, Andreas Grassauer, Janina Auth, Ulrich Schubert, Eva Prieschl-Grassauer

PLOS ONE, doi:10.1371/journal.pone.0237480

In the absence of a vaccine and other effective prophylactic or therapeutic countermeasures the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) remains a significant public health threat. Attachment and entry of coronaviruses including SARS-CoV-2 is mainly mediated by the spike glycoprotein. Here, we show that iota-carrageenan can inhibit the cell entry of the SARS-CoV-2 spike pseudotyped lentivirus in a dose dependent manner. SARS-CoV-2 spike pseudotyped lentivirus particles were efficiently neutralized with an IC 50 value of 2.6 μg/ml iota-carrageenan. Experiments with patient isolated wild type SARS-CoV-2 virus showed an inhibition of replication in a similar range. In vitro data on iotacarrageenan against various Rhino-and endemic Coronaviruses showed similar IC 50 values and translated readily into clinical effectiveness when a nasal spray containing iota-carrageenan demonstrated a reduction of severity and duration of symptoms of common cold caused by various respiratory viruses. Accordingly, our in vitro data on SARS-CoV-2 spike pseudotyped lentivirus and replication competent SARS-CoV-2 suggest that administration of iota-carrageenan may be an effective and safe prophylaxis or treatment for SARS-CoV-2 infections.

Supporting information S1 Author Contributions Conceptualization: Martina Morokutti-Kurz, Andreas Grassauer, Ulrich Schubert, Eva Prieschl-Grassauer. Data curation: Martina Morokutti-Kurz, Maria Fro ¨ba, Philipp Graf, Maximilian Große, Janina Auth, Ulrich Schubert, Eva Prieschl-Grassauer. Formal analysis: Martina Morokutti-Kurz, Maria Fro ¨ba, Philipp Graf, Maximilian Große, Andreas Grassauer, Janina Auth. Funding acquisition: Andreas Grassauer, Ulrich Schubert, Eva Prieschl-Grassauer. Investigation: Maria Fro ¨ba, Philipp Graf, Maximilian Große, Janina Auth. Methodology: Martina Morokutti-Kurz, Maria Fro ¨ba, Janina Auth, Ulrich Schubert. Project administration: Janina Auth, Eva Prieschl-Grassauer. Resources: Andreas Grassauer, Janina Auth, Ulrich Schubert, Eva Prieschl-Grassauer. Software: Eva Prieschl-Grassauer. Supervision: Ulrich Schubert. Validation: Eva Prieschl-Grassauer. Visualization: Eva Prieschl-Grassauer. Writing -original draft: Martina Morokutti-Kurz, Andreas Grassauer, Ulrich Schubert, Eva Prieschl-Grassauer. Writing -review & editing: Martina Morokutti-Kurz, Maria Fro ¨ba, Maximilian Große, Andreas Grassauer, Ulrich Schubert, Eva Prieschl-Grassauer.

References

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Dogan, Kozhaya, Placek, Gunter, Yigit et al., Novel SARS-CoV-2 specific antibody and neutralization assays reveal wide range of humoral immune response during COVID-19, medRxiv, doi:10.1101/2020.07.07.20148106

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Eccles, Winther, Johnston, Robinson, Trampisch et al., Efficacy and safety of iotacarrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial, Respir Res, doi:10.1186/s12931-015-0281-8

Fazekas, Eickhoff, Pruckner, Vollnhofer, Fischmeister et al., Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold, BMC Complement Altern Med, doi:10.1186/1472-6882-12-147

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Große, Ruetalo, Businger, Rheber, Setz et al., Evidence That Quinine Exhibits Antiviral Activity against SARS-CoV-2 Infection In Vitro, Preprints

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Koenighofer, Lion, Bodenteich, Prieschl-Grassauer, Grassauer et al., Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials, Multidiscip Respir Med, doi:10.1186/2049-6958-9-57

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Morokutti-Kurz, Konig-Schuster, Koller, Graf, Graf et al., The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model 4944, PLoS ONE, doi:10.1371/journal.pone.0128794

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