The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 Brno CZ 613 00 Czech Republic

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 Brno CZ 613 00 Czech Republic Central European Institute of Technology Brno University of Technology Technicka 3058 10 Brno CZ 616 00 Czech Republic

Institute of Virology Slovak Academy of Sciences Dubravska cesta 9 84505 Bratislava Slovak Republic

Laboratory of Tumour Biology Institute of Animal Physiology and Genetics Academy of Sciences of the Czech Republic Libechov CZ 277 21 Czech Republic

Wool and Knitting Research Institute Brno Sujanovo namesti 3 Brno CZ 602 00 Czech Republic