Anti-influenza A virus activity of an acidic polysaccharide from a blue-green alga Nostoc flagelliforme

Influenza has been continued over a long time to be a significant public health concern, since annual epidemics by the pathogen are responsible for serious morbidity and mortality. Especially, the emergence of highly pathogenic avian influenza A virus (IFV) has lately become of major concern after it was documented to cause severe respiratory diseases and death in humans.

We have recently reported on in vitro anti-IFV activity of nostoflan, a novel polysaccharide isolated from N. flagelliforme [1]. In this study, in vivo efficacy of nostoflan was evaluated in reducing the replication of IFV using murine models. When the polysaccharide was intranasally administered to IFV-infected mice, it significantly reduced the virus production in both respiratory tract and the lung as compared with no-drug control.

In the previous study, nostoflan was found to inhibit the binding of herpes simplex virus to host cells [2]. Anti-IFV target of this compound was also shown to be the inhibition of virus binding to cells in the present study. This antiviral target is different from that of oseltamivir, a neuraminidase (NA) inhibitor. Thus, we have evaluated the combination of nostoflan and oseltamivir in suppressing IFV replication. In vitro experiments demonstrated that the combined treatment synergistically reduced virus yields at low concentrations of each compound. When IFV-infected mice were treated with intranasal nostoflan combined with oral oseltamivir, nostoflan markedly suppressed virus production in the presence of lower doses of oseltamivir.

From these results, nostoflan is worthy of further exploration for its potential of single use or combination therapy with NA inhibitors in the treatment of IFV infectious diseases.

References: 1. Kanekiyo, K. et al. (2005)J. Nat. Prod. 68: 1037–1041.

2. Kanekiyo, K. et al (2007) Biol. Pharm. Bull. 30: 1573–1575.