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Carrageenans and the Carrageenan-Echinochrome Complex as Anti-SARS-CoV-2 Agents

Krylova et al., International Journal of Molecular Sciences, doi:10.3390/ijms26136175, Jun 2025
https://c19early.org/krylova.html
In Vitro and In Silico study showing that carrageenans and a carrageenan-echinochrome complex inhibit SARS-CoV-2 replication in Vero E6 cells. Authors isolated different types of carrageenans (kappa, lambda, kappa/beta) from red algae and used molecular docking to demonstrate their interactions with SARS-CoV-2's receptor-binding domain (RBD) and human ACE2 receptor through hydrogen bonding and ionic interactions. Kappa-carrageenan exhibited the strongest binding affinity to ACE2 and the most significant antiviral effect with a selective index (SI) of 33. The kappa-carrageenan/echinochrome complex showed even higher antiviral activity, with the strongest virucidal effect against SARS-CoV-2 particles (SI above 70) and 45% reduction in viral RNA levels. The complex was most effective when directly applied to virus particles before infection, suggesting a direct virucidal mechanism. All tested carrageenans demonstrated low cytotoxicity with CC50 values above 2000 μg/mL.
15 preclinical studies support the efficacy of iota-carrageenan for COVID-19:
Krylova et al., 26 Jun 2025, peer-reviewed, 8 authors, study period 11 March, 2020 - 5 May, 2023. Contact: krylovanatalya@gmail.com (corresponding author), olga_iun@inbox.ru, niiem_vl@mail.ru, adorob@mail.ru, kravchenko_89@mail.ru, galin56@mail.ru, glazunov@piboc.dvo.ru, imyer@mail.ru.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Carrageenans and the Carrageenan-Echinochrome Complex as Anti-SARS-CoV-2 Agents
Natalya V Krylova, Anna O Kravchenko, Galina N Likhatskaya, Olga V Iunikhina, Valery P Glazunov, Tatyana S Zaporozhets, Mikhail Y Shchelkanov, Irina M Yermak
International Journal of Molecular Sciences, doi:10.3390/ijms26136175
The diversity of structural types of carrageenans (CRGs)-sulfated polysaccharides of red algae-determines their different biological activities. The different types of CRGs (kappa, lambda, kappa/beta-CRGs) were isolated from the red algae of the Pacific coast. Molecular docking was performed to determine potential interactions of CRGs with the receptorbinding domain (RBD) of SARS-CoV-2 and its cellular receptor-angiotensin-converting enzyme type 2 (ACE2). CRGs interacted with ACE2 and RBD via hydrogen bonding and ionic interactions. The strongest binding affinity of CRGs and ACE2 was observed for kappa-CRG. Molecular docking was confirmed by results studying the effects of CRGs against SARS-CoV-2 in vitro. The ability of CRGs, as well as the complex CRG with sea urchin echinochrome (Ech), to inhibit SARS-CoV-2 replication in Vero E6 cells was studied using cytopathic effect (CPE) inhibition and RT-PCR assays. The simultaneous treatment of cells with CRGs and the virus revealed that kappa-CRG exhibited the most significant antiviral effect among all the polysaccharides, with a selective index (SI) of 33. The kappa-CRG/Ech complex exhibited the highest virucidal effect on SARS-CoV-2 particles with an SI above 70 (more than two times higher than that of CRG and Ech) and reduced viral RNA levels by 45% (IC = 45%). Our results illustrate that CRGs and kappa-CRG/Ech complex can act as protective agents against SARS-CoV-2.
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DOI record: { "DOI": "10.3390/ijms26136175", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms26136175", "abstract": "<jats:p>The diversity of structural types of carrageenans (CRGs)—sulfated polysaccharides of red algae—determines their different biological activities. The different types of CRGs (kappa, lambda, kappa/beta-CRGs) were isolated from the red algae of the Pacific coast. Molecular docking was performed to determine potential interactions of CRGs with the receptor-binding domain (RBD) of SARS-CoV-2 and its cellular receptor—angiotensin—converting enzyme type 2 (ACE2). CRGs interacted with ACE2 and RBD via hydrogen bonding and ionic interactions. The strongest binding affinity of CRGs and ACE2 was observed for kappa-CRG. Molecular docking was confirmed by results studying the effects of CRGs against SARS-CoV-2 in vitro. The ability of CRGs, as well as the complex CRG with sea urchin echinochrome (Ech), to inhibit SARS-CoV-2 replication in Vero E6 cells was studied using cytopathic effect (CPE) inhibition and RT-PCR assays. The simultaneous treatment of cells with CRGs and the virus revealed that kappa-CRG exhibited the most significant antiviral effect among all the polysaccharides, with a selective index (SI) of 33. The kappa-CRG/Ech complex exhibited the highest virucidal effect on SARS-CoV-2 particles with an SI above 70 (more than two times higher than that of CRG and Ech) and reduced viral RNA levels by 45% (IC = 45%). Our results illustrate that CRGs and kappa-CRG/Ech complex can act as protective agents against SARS-CoV-2.</jats:p>", "alternative-id": [ "ijms26136175" ], "author": [ { "ORCID": "https://orcid.org/0000-0002-9048-6803", "affiliation": [ { "name": "G.P. 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