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

https://c19early.org/morokuttikurz.html

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

Important missing comments or errors? Let us know.

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

Corman, Landt, Kaiser, Molenkamp, Meijer et al., Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Euro Surveill, doi:10.2807/1560-7917.ES.2020.25.3.2000045

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

Eccles, Iota-Carrageenan as an Antiviral Treatment for the Common Cold, The Open Virology Journal

Eccles, Meier, Jawad, Weinmu ¨llner R, Grassauer et al., Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold, Respir Res, doi:10.1186/1465-9921-11-108

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

Gates, Responding to Covid-19-A Once-in-a-Century Pandemic, N Engl J Med, doi:10.1056/NEJMp2003762

Grassauer, Weinmu ¨llner R, Meier, Pretsch, Prieschl-Grassauer et al., Iota-Carrageenan is a potent inhibitor of rhinovirus infection, Virol J, doi:10.1186/1743-422X-5-107

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

Hoffmann, Kleine-Weber, Schroeder, Kru ¨ger, Herrler et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell, doi:10.1016/j.cell.2020.02.052

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

Leibbrandt, Meier, Ko ¨nig-Schuster, Weinmu ¨llner R, Kalthoff et al., Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection, PLoS One, doi:10.1371/journal.pone.0014320

Long, Tang, Shi, Li, Deng et al., Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections, Nat Med, doi:10.1038/s41591-020-0965-6

Ludwig, Enzenhofer, Schneider, Rauch, Bodenteich et al., Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial, Respir Res, doi:10.1186/1465-9921-14-124

Mcintosh, Dees, Becker, Kapikian, Chanock, Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease, Proc Natl Acad Sci U.S.A, doi:10.1073/pnas.57.4.933

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

Perlman, Another Decade, Another Coronavirus, N Engl J Med, doi:10.1056/NEJMe2001126

Reed, Muench, A simple method of estimating fifty percent endpoints, Am J Hyg

Wu, Zhao, Yu, Chen, Song, A new coronavirus associated with human respiratory disease in China, Nature, doi:10.1038/s41586-020-2008-3

Zhu, Zhang, Li, Yang, Song, A Novel Coronavirus from Patients with Pneumonia in China, 2019, N Engl J Med, doi:10.1056/NEJMoa2001017

DOI record: { "DOI": "10.1371/journal.pone.0237480", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0237480", "abstract": "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 IC50 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 iota-carrageenan against various Rhino- and endemic Coronaviruses showed similar IC50 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.", "author": [ { "affiliation": [], "family": "Morokutti-Kurz", "given": "Martina", "sequence": "first" }, { "affiliation": [], "family": "Fröba", "given": "Maria", "sequence": "additional" }, { "affiliation": [], "family": "Graf", "given": "Philipp", "sequence": "additional" }, { "affiliation": [], "family": "Große", "given": "Maximilian", "sequence": "additional" }, { "affiliation": [], "family": "Grassauer", "given": "Andreas", "sequence": "additional" }, { "affiliation": [], "family": "Auth", "given": "Janina", "sequence": "additional" }, { "affiliation": [], "family": "Schubert", "given": "Ulrich", "sequence": "additional" }, { "affiliation": [], "family": "Prieschl-Grassauer", "given": "Eva", "sequence": "additional" } ], "container-title": "PLOS ONE", "container-title-short": "PLoS ONE", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2021, 2, 17 ] ], "date-time": "2021-02-17T18:34:13Z", "timestamp": 1613586853000 }, "deposited": { "date-parts": [ [ 2021, 2, 17 ] ], "date-time": "2021-02-17T18:34:39Z", "timestamp": 1613586879000 }, "editor": [ { "affiliation": [], "family": "Polyak", "given": "Stephen J.", "sequence": "first" } ], "funder": [ { "DOI": "10.13039/501100004955", "award": [ "880687" ], "doi-asserted-by": "publisher", "name": "Österreichische Forschungsförderungsgesellschaft" } ], "indexed": { "date-parts": [ [ 2024, 5, 8 ] ], "date-time": "2024-05-08T13:53:49Z", "timestamp": 1715176429581 }, "is-referenced-by-count": 74, "issue": "2", "issued": { "date-parts": [ [ 2021, 2, 17 ] ] }, "journal-issue": { "issue": "2", "published-online": { "date-parts": [ [ 2021, 2, 17 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 2, 17 ] ], "date-time": "2021-02-17T00:00:00Z", "timestamp": 1613520000000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0237480", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0237480", "prefix": "10.1371", "published": { "date-parts": [ [ 2021, 2, 17 ] ] }, "published-online": { "date-parts": [ [ 2021, 2, 17 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "DOI": "10.1056/NEJMoa2001017", "article-title": "A Novel Coronavirus from Patients with Pneumonia in China, 2019", "author": "N Zhu", "doi-asserted-by": "crossref", "first-page": "727", "journal-title": "N Engl J Med", "key": "pone.0237480.ref001", "volume": "382", "year": "2020" }, { "DOI": "10.1038/s41586-020-2008-3", "article-title": "A new coronavirus associated with human respiratory disease in China", "author": "F Wu", "doi-asserted-by": "crossref", "first-page": "265", "journal-title": "Nature", "key": "pone.0237480.ref002", "volume": "579", "year": "2020" }, { "DOI": "10.1056/NEJMe2001126", "article-title": "Another Decade, Another Coronavirus", "author": "S. Perlman", "doi-asserted-by": "crossref", "first-page": "760", "journal-title": "N Engl J Med", "key": "pone.0237480.ref003", "volume": "382", "year": "2020" }, { "DOI": "10.1056/NEJMp2003762", "article-title": "Responding to Covid-19—A Once-in-a-Century Pandemic", "author": "B. Gates", "doi-asserted-by": "crossref", "first-page": "1677", "journal-title": "N Engl J Med", "key": "pone.0237480.ref004", "volume": "382", "year": "2020" }, { "DOI": "10.1016/j.cell.2020.02.052", "article-title": "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor", "author": "M Hoffmann", "doi-asserted-by": "crossref", "first-page": "271", "journal-title": "Cell", "key": "pone.0237480.ref005", "volume": "181", "year": "2020" }, { "DOI": "10.2174/1874357902014010009", "article-title": "Iota-Carrageenan as an Antiviral Treatment for the Common Cold", "author": "R. Eccles", "doi-asserted-by": "crossref", "first-page": "9", "issue": "14", "journal-title": "The Open Virology Journal", "key": "pone.0237480.ref006", "volume": "2020", "year": "2020" }, { "DOI": "10.1186/1743-422X-5-107", "article-title": "Iota-Carrageenan is a potent inhibitor of rhinovirus infection", "author": "A Grassauer", "doi-asserted-by": "crossref", "journal-title": "Virol J", "key": "pone.0237480.ref007", "volume": "5", "year": "2008" }, { "DOI": "10.1371/journal.pone.0014320", "article-title": "Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection", "author": "A Leibbrandt", "doi-asserted-by": "crossref", "journal-title": "PLoS One", "key": "pone.0237480.ref008", "volume": "5", "year": "2010" }, { "DOI": "10.1371/journal.pone.0128794", "article-title": "The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model 4944", "author": "M Morokutti-Kurz", "doi-asserted-by": "crossref", "first-page": "e0128794", "journal-title": "PLoS ONE", "key": "pone.0237480.ref009", "volume": "10", "year": "2015" }, { "DOI": "10.1186/1465-9921-11-108", "article-title": "Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold", "author": "R Eccles", "doi-asserted-by": "crossref", "first-page": "108", "journal-title": "Respir Res", "key": "pone.0237480.ref010", "volume": "11", "year": "2010" }, { "DOI": "10.1186/1472-6882-12-147", "article-title": "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", "author": "T Fazekas", "doi-asserted-by": "crossref", "first-page": "147", "journal-title": "BMC Complement Altern Med", "key": "pone.0237480.ref011", "volume": "12", "year": "2012" }, { "DOI": "10.1186/2049-6958-9-57", "article-title": "Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials", "author": "M Koenighofer", "doi-asserted-by": "crossref", "first-page": "57", "journal-title": "Multidiscip Respir Med", "key": "pone.0237480.ref012", "volume": "9", "year": "2014" }, { "DOI": "10.1186/1465-9921-14-124", "article-title": "Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial", "author": "M Ludwig", "doi-asserted-by": "crossref", "first-page": "124", "journal-title": "Respir Res", "key": "pone.0237480.ref013", "volume": "14", "year": "2013" }, { "DOI": "10.1186/s12931-015-0281-8", "article-title": "Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial", "author": "R Eccles", "doi-asserted-by": "crossref", "first-page": "121", "journal-title": "Respir Res", "key": "pone.0237480.ref014", "volume": "16", "year": "2015" }, { "article-title": "Evidence That Quinine Exhibits Antiviral Activity against SARS-CoV-2 Infection In Vitro", "author": "M Große", "first-page": "2020070102", "journal-title": "Preprints", "key": "pone.0237480.ref015", "year": "2020" }, { "article-title": "A simple method of estimating fifty percent endpoints", "author": "LJ Reed", "first-page": "493", "journal-title": "Am J Hyg", "key": "pone.0237480.ref016", "year": "1938" }, { "DOI": "10.2807/1560-7917.ES.2020.25.3.2000045", "article-title": "Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR", "author": "VM Corman", "doi-asserted-by": "crossref", "journal-title": "Euro Surveill", "key": "pone.0237480.ref017", "volume": "25", "year": "2020" }, { "DOI": "10.1073/pnas.57.4.933", "article-title": "Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease", "author": "K McIntosh", "doi-asserted-by": "crossref", "first-page": "933", "journal-title": "Proc Natl Acad Sci U.S.A", "key": "pone.0237480.ref018", "volume": "57", "year": "1967" }, { "article-title": "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections", "author": "Q-X Long", "journal-title": "Nat Med", "key": "pone.0237480.ref019", "year": "2020" }, { "article-title": "Novel SARS-CoV-2 specific antibody and neutralization assays reveal wide range of humoral immune response during COVID-19", "author": "M Dogan", "journal-title": "medRxiv", "key": "pone.0237480.ref020", "year": "2020" } ], "reference-count": 20, "references-count": 20, "relation": {}, "resource": { "primary": { "URL": "https://dx.plos.org/10.1371/journal.pone.0237480" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1371/journal.pone.corrections_policy", "volume": "16" }

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0