Development of new therapeutic strategies against influenza virus
The annual seasonal flu caused by influenza viruses can affect 5 to 15 % of the population. In addition to vaccination, the use of antiviral drugs in the treatment and prevention allows the control of influenza virus infection. So far, two classes of antiviral drugs have been approved for influenza treatment, one to inhibit the uncoating step (M2 inhibitors), and the other to prevent the release of progeny virions (NA inhibitors). However, the emergence and circulation of M2 inhibitor resistant viruses at high frequencies have restricted the use of these inhibitors. Neuraminidase inhibitor resistance among circulating influenza viruses has emerged since the 2008 – 2009 season. The development of new classes of antiviral agents is crucial in the fight against influenza virus. In recent years, many molecules belonging to a large group of compounds known as carbohydrates (oligosaccharides/polysaccharides) have been revealed essential for various biological activities. The establishment of carbohydrate-based antiviral agents is, therefore, a highly promising strategy. In order to evaluate the potentially anti-influenza molecules derived from carbohydrates, we have performed a screening from a library of 245 polysaccharides and oligosaccharides. These compounds were extracted mainly from plants and algae. Several active molecules of different families have been identified. Among them, the sulphated oligosaccharide 152, belonging to the family of arabinogalactane, was found to be highly active toward both influenza virus A and B in vitro. This oligosaccharide was purified from the green algal species Codium fragile. The study of the 152 mechanism suggests that this oligosaccharide can cooperatively inhibit both viral HA binding activity and NA catalytic activity