title: Influenza Virus H1N1 inhibition by serine protease inhibitor (serpin) antithrombin III.
abstract: Endogenous serine protease inhibitors (serpins) are anti-inflammatory mediators with multiple biologic functions. Serpins are also part of the early innate immune response to viral infection that includes mannose binding lectins, soluble CD14, defensins and antimicrobial peptides. Recently, serpin antithrombin III (ATIII) was shown to have broad-spectrum antiviral activity against HIV, HSV and HCV. We tested ATIII's antiviral activity against a variety of influenza virus strains. In our studies we found strongin vitroinhibition of influenza virus A H1N1 isolates. Our data also demonstrate that ATIII potency was more than 100-fold that of ribavirin. We also found that inhibition was dependent on viral hemagglutinin with decreasing efficacy in the order of H1N1 > H3N2 > H5N1 >> Flu B.In vivoefficacy is currently still lacking demonstrating need for more advanced delivery methods for this biomolecule. Understanding how ATIII regulates influenza virus inhibition may reveal new avenues for therapeutic interventions.
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, Utah, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, Utah, USA.
authors.forename: Brett L
authors.initials: BL
authors.lastname: Hurst
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, Utah, USA.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Day
authors.affiliation: Acceleration BioPharmaceuticals, Inc. Woburn, MA, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Geiben-Lynn
keywords: Antithrombin III; Serpin; hemagglutinin dependent; influenza virus H1N1