Mechanism of Action of Flufirvitide, a Peptide Inhibitor of Influenza Virus Infection

Abstract

Influenza is an infectious disease typically transmitted through the air. It is responsible for seasonal epidemics affecting millions of people, and sporadic global pandemics. Influenza infection is a membrane fusion‐dependant process, occurring in the endosome of the host cell after viral binding and endocytosis. The virus‐host membrane fusion process is mediated by hemagglutinin (HA), a viral surface glycoprotein. Studies show that when the virus is subjected to low pH in the endosome, the HA protein partially unfolds and changes conformation, exposing the fusion initiation region (FIR). A 16 amino acid peptide sequence (Flufirvitide) derived from the fusion initiation region of the HA protein has shown effective inhibition of influenza virus infection.  It is hypothesized that there is an interaction between the peptide and the FIR which inhibits fusion of the virus to the host cell. Plaque inhibition assays and animal studies show high efficacy of the peptide against the virus. We are currently developing biochemical and biophysical assays to study the interaction between Flufirvitide and HA. Circular Dichroism studies show that the peptide has a random coil conformation at pH 7 and higher. To elucidate the mechanism of fusion inhibition, the interaction between peptide and HA is being investigated with immunodetection, immunoprecipitation, and florescence techniques. Additionally, binding and interaction of the peptide with the intact virus is being studied by using Cryo‐electron microscopy.

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