Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus

Abstract

Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. Here we have dissected bLf into its C- and N-lobes and show that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited. By far-western blotting and sequencing studies, we demonstrate that bLf C-lobe strongly binds to the HA₂ region of viral hemagglutinin, precisely the highly conserved region containing the fusion peptide. By molecular docking studies, three C-lobe fragments were identified which inhibited virus hemagglutination and infection at fentomolar concentration range. Besides contributing to explain the broad anti-influenza activity of bLf, our findings lay the foundations for exploiting bLf fragments as source of potential anti-influenza therapeutics.

Keywords:

• Influenza
• Bovine lactoferrin
• C-lobe
• Peptides
• Antiviral

We are grateful to Dr Isabella Donatelli (ISS, Italy) for viral isolates.

This work was supported by a grant from Ministero della Salute-Istituto Superiore di Sanità- within the Research Project: ‘Studio e sviluppo di nuovi farmaci antivirali contro infezioni A-H1N1’.