Karoline Droebner 1), Holger Kiesewetter 2), Stephan Ludwig 3) and Oliver Planz 1)
1) Friedrich-Loeffler-Institut, Institute of Immunology, Paul-Ehrlich Str. 28, 72076 Tübingen, Germany 2) Charité Universitätsmedizin Berlin, Institut für Transfusionsmedizin Campus Charité Mitte, Luisenstr. 65, 10117 Berlin, Germany 3) Westfaelische-Wilhelms-Universitaet Münster, Zentrum für Molekularbiologie der Entzündung, Institute of Molecular Virology (IMV),Von Esmarch-Str. 56, 48159 Muenster, Germany
Influenza still represents a major threat to human health. The appearance of highly pathogenic avian influenza viruses of the H5N1 subtype being able to infect humans reveals the urgent need for new and efficient countermeasures against this disease. Several antiviral compounds have been developed against influenza virus; their long-term efficacy is often limited, because of their toxicity or the emergence of drug-resistant virus mutants. Moreover, neuraminidase inhibitors the most common anti-influenza agents are less effective against new H5N1 isolates. In this regard, we were able to show that a polyphenol rich plant extract from a special variety of Cistus incanus named Cystus052 exhibits antiviral activity against influenza viruses in vitro, in a mouse model and a randomized, placebo controlled clinical study. The recovery from clinical symptoms was 2.5 days faster in the Cystus052 group compared to patients taken the placebo. The protective effect of Cystus052 appears to be mainly due to binding of the polymeric polyphenol components of the extract to the virus surface, thereby inhibiting binding of the hemagglutinin to cellular receptors. The antiviral potential of Cystus052 against seven H5N1 viruses by IC50, EC50, Km, Vmax and Ki values indicated that Cystus052 was much more potent than oseltamivir. In addition, using an in vitro infectivity inhibition assay we found that a single treatment of Cystus052 was up to 100-fold more effective against these H5N1 viruses compared to oseltamivir, during the first 24 hours after infection. We conclude that Cystus052 given prior to infection might be an effective antiviral with prophylactic potential against influenza viruses including A/H5N1.