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Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2.

ABSTRACT: Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (?-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC₅₀ values ranging from 0.3 to 1.4 ?g/ml, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an EC₅₀ value of 0.9?±?1.1 ?g/ml. No toxicity to the host cells was observed at concentrations up to 300 ?g/ml. Plaque titration and western blot analysis verified that ?-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing virus entry. Moreover, its intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, ?-CGN could be a promising antiviral agent for preventing infection with several respiratory viruses.

SUBMITTER: Jang Y

PROVIDER: S-EPMC7804421 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2.

Jang Yejin Y Shin Heegwon H Lee Myoung Kyu MK Kwon Oh Seung OS Shin Jin Soo JS Kim Yong-Il YI Kim Chan Woo CW Lee Hye-Ra HR Kim Meehyein M

Scientific reports 20210112 1

Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC<sub>50</sub> values ranging from 0.3 to 1.4 μg/ml, as well as currently circ ...[more]

PMID: 33436985

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Project description:Some respiratory viruses can cause a viral interference through the activation of the interferon (IFN) pathway that reduces the replication of another virus. Epidemiological studies of coinfections between SARS-CoV-2 and other respiratory viruses have been hampered by non-pharmacological measures applied to mitigate the spread of SARS-CoV-2 during the COVID-19 pandemic. With the ease of these interventions, SARS-CoV-2 and influenza A viruses can now co-circulate. It is thus of prime importance to characterize their interactions. In this work, we investigated viral interference effects between an Omicron variant and a contemporary influenza A/H3N2 strain, in comparison with an ancestral SARS-CoV-2 strain and the 2009 pandemic influenza A/H1N1 virus. We infected nasal human airway epitheliums with SARS-CoV-2 and influenza, either simultaneously or 24 h apart. Viral load was measured by RT-qPCR and IFN-α/β/λ1/λ2 proteins were quantified by immunoassay. Expression of four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) was also measured by RT-droplet digital PCR. Additionally, susceptibility of each virus to IFN-α/β/λ2 recombinant proteins was determined. Our results showed that influenza A, and especially A/H3N2, interfered with both SARS-CoV-2 viruses, but that SARS-CoV-2 did not significantly interfere with A/H3N2 or A/H1N1. Consistently with these results, influenza, and particularly the A/H3N2 strain, caused a higher production of IFN proteins and expression of ISGs than SARS-CoV-2. SARS-CoV-2 induced a marginal IFN production and reduced the IFN response during coinfections with influenza. All viruses were susceptible to exogenous IFNs, with the ancestral SARS-CoV-2 and Omicron being less susceptible to type I and type III IFNs, respectively. Thus, influenza A causes a viral interference towards SARS-CoV-2 most likely through an IFN response. The opposite is not necessarily true, and a concurrent infection with both viruses leads to a lower IFN response. Taken together, these results help us to understand how SARS-CoV-2 interacts with another major respiratory pathogen.

Project description:ObjectiveThere 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.MethodsPubMed/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.ResultsCarrageenan 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.ConclusionThough 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.

Dataset Information

Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2.

Publications

Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2.

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