The antiviral activity of iota-, kappa-, and lambda-carrageenan against COVID-19: A critical review

Abstract

Objective There is no specific antiviral treatment available for coronavirus disease 2019 (COVID-19). Among the possible natural constituents is carrageenan, a polymer derived from marine algae that possesses a variety of antiviral properties. The purpose of this review was to summarize the evidence supporting carrageenan subtypes' antiviral activity against the emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Methods PubMed/MEDLINE and Google Scholar searches were conducted for publications using the terms ‘carrageenan’, ‘iota carrageenan’, ‘kappa carrageenan’, lambda-carrageenan’, 'coronavirus', ‘common cold’, 'rhinovirus', and ‘SARS-CoV-2′ search was also done in grey literature to increase our understanding. A search for the word “carrageenan” was also carried out. Most of the publications were discussed in narrative. Results Carrageenan has been shown to have potent antiviral activity against both coronaviruses (coronavirus NL63, SARS-CoV-2) and non-coronaviruses such as dengue virus, herpes simplex virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, sindbis virus, human immunodeficiency virus, influenza virus, human papillomavirus, rabies virus, junin virus, tacaribe virus, African swine fever, bovine herpes virus, suid herpes virus, and rhinovirus. No in vivo study has been conducted using carrageenan as an anti-SARS-CoV-2 agent. The majority of the in vivo research was done on influenza, a respiratory virus that causes common cold together with coronavirus. Thus, various clinical trials were conducted to determine the transferability of these in vitro data to clinical effectiveness against SARS-CoV-2. When combined with oral ivermectin, nasally administered iota-carrageenan improved outcome in COVID-19 patients. It is still being tested in clinics for single-dose administration. Conclusion Though the carrageenan exhibited potent antiviral activity against SARS-CoV-2 and was used to treat COVID-19 under emergency protocol in conjunction with oral medications such as ivermectin, there is no solid evidence from clinical trials to support its efficacy. Thus, clinical trials are required to assess its efficacy for COVID-19 treatment prior to broad application.

Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta

“…It was shown previously that, in addition to iota-carrageenan, kappa-and lambdacarrageenan also exhibit antiviral activity against the SARS-CoV-2 Wuhan type [38][39][40]. The polysaccharides differ in their location and number of sulfate moieties on the hexose scaffold sceleton and thus contain one (kappa), two (iota) or three (lambda) negatively charged sulfate ester groups per disaccharide repeating unit [51,52]. Carrageenan homopolymers do usually not occur isolated in nature.…”

Iota-Carrageenan Prevents the Replication of SARS-CoV-2 in a Human Respiratory Epithelium Cell Line in vitro

“…Different articles have been published that raise the hypothetical usefulness of nasal sprays with carrageenan for both prevention and treatment of COVID-19 (38)(39)(40), although some clinical trials are underway (Carrageenan Nasal Spray for COVID-19 Prophylaxis [ICE-COVID], Swansea University, ClinicalTrials.gov Identifier: NCT04590365; Prophylactic Treatment With Carragelose Nasal Spray to Prevent SARS-CoV-2, COVID-19, Infections in Health Care Workers, Marinomed Biotech AG, ClinicalTrials.gov Identifier: NCT04681001). So far, a unique trial has been completed, and its results published in a peer-reviewed journal indexed in PubMed (36).…”

Bioactive Carbohydrate Polymers—Between Myth and Reality

“…The great potential of polysaccharides from different sources as antiviral agents is undeniable, especially when the origin is seaweeds. Alginate, fucoidan, and laminarin, typically obtained from brown algae [ 95 , 256 , 257 , 258 , 259 , 262 , 271 , 275 , 287 ], carrageenan and galactans from red algae [ 257 , 258 , 261 , 262 , 263 , 264 , 265 ], and ulvan from green algae [ 262 , 266 ], often present antiviral activity against several viruses ( Table 3 ). Indeed, this recognized biological activity immediately aroused the interest of the scientific community to search for solutions against the new SARS-CoV-2 virus responsible for causing COVID-19 [ 264 , 271 , 288 ].…”