The Anti-Viral Role and Therapeutic Potential of Novel Seaweed-Derived Compounds

Objectives: Influenza viruses are segmented single stranded negative sense RNA (-ssRNA) viruses in the Orthomyxoviridae family and cause respiratory infections. Influenza A viruses (IAV) are responsible for the majority of human disease and 5 pandemics since 1889, the most recent of which was 2009 and the most lethal in 1918 with over 50 million recorded deaths worldwide. Vaccines and antiviral drugs are available however these are often ineffective due to rapid virus evolution. Methods: This study focuses on an Enriched seaweed extracts (ESE) isolated from the brown seaweed Ascophyllum Nodosum by the industrial partner Byotrol. ESE was screened for antiviral activity by plaque reduction assays against IAV H1N1, H3N2 subtypes and rhinovirus (RV), which was used as a non-enveloped model to test for broad-acting activity. Time of addition assays, immunofluorescent imaging and FACs analysis were used to help determine the mode of action. The therapeutic potential of the ESE was then explored using differentiated human bronchiole epithelial cells at the air liquid interphase and in a murine model challenged with IAV. Results: The data indicates ESE primarily interacts directly with virions, preventing virus cell binding and internalisation. Interestingly, ESE also inhibits early and late stage of the influenza lifecycle when treatment occurs after cell binding, which was not seen with rhinovirus. This inhibitory effect appears to prevent trafficking of viral RNPs to the cell nucleus and release of progeny virus by targeting neuraminidase activity. Intranasal administration of ESE in mice infected with IAV or at the time of infection reduced viral load in lung tissue. Discussion: ESE may be a promising broad acting antiviral agent in the treatment or prophylactic treatment of respiratory infections through the inhibition of virus cell binding and internalisation.