Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model

Alsaidi et al., Marine Drugs, doi:10.3390/md19080418

Jul 2021

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In Vitro and In Silico analysis showing SARS-CoV-2 antiviral activity of carageenan, and synergistic activity from the combination of carrageenan and griffithsin.

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.

Alsaidi et al., 26 Jul 2021, peer-reviewed, 12 authors.

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

This Paper Iota-carragee..All

Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model

Sahar Alsaidi, Nadjet Cornejal, Oneil Mahoney, Claudia Melo, Neeharika Verma, Thierry Bonnaire, Theresa Chang, Barry R O’keefe, James Sailer, Thomas M Zydowsky, Natalia Teleshova, José A Fernández Romero

Marine Drugs, doi:10.3390/md19080418

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC 50 ) and half-maximal effective concentration (EC 50 ) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC 50 /EC 50 ) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC 50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC 50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.

References

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Who, Coronavirus Disease (COVID-19) Pandemic

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