The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model

Abstract

BackgroundCarrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo.Principal FindingsWe show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection.ConclusionA nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.

A review of extractions of seaweed hydrocolloids: Properties and applications

“…As an example, kappa (κ)-carrageenan is used as immobilizer for Streptomyces aureofacies and Pseudomonas dacunhae cells to improve the production of tetracycline and chlorotetracycline (antibiotic) and D-aspartic acid and L-alanine in drug production [52]. Moreover, carrageenan proved to inhibit the attachment of viruses such as the human papillomavirus, dengue virus, influenza A, and herpes virus [8,[52][53][54].…”

Iota-carrageenan and Xylitol inhibit SARS-CoV-2 in cell culture

“…In all cases the antiviral action of iota-carrageenan is more effective, when administrated preventively or in the early stages of disease and has shown synergy with other antiviral agents. Studies performed on adults and children with common cold demonstrate effectivity of iotacarrageenan nasal spray to alleviate the clinical symptoms and shorten their duration, as well as to decrease the viral load of nasopharyngeal specimens and the relapses during the follow-up period [14,15,16,18,19,20]. Iota-carrageenan-containing nasal sprays are already on the market in several countries in the world.…”

SARS-CoV-2 in-vitro neutralization assay reveals inhibition of virus entry by iota-carrageenan

“…The antiviral activity of iota-carrageenan has been demonstrated in vitro against a variety of respiratory viruses [7][8][9]. The transferability of these in vitro data into clinical effectiveness was evaluated in four clinical trials [10][11][12][13][14].…”