Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins

Eugenia Leikina¹, Helene Delanoe-Ayari¹, Kamran Melikov¹, Myoung-Soon Cho², Andrew Chen¹, Alan J Waring³, Wei Wang³, Yongming Xie⁴, Joseph A Loo^3, 4, Robert I Lehrer³ & Leonid V Chernomordik¹

¹  Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1855, USA.

²  Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1855, USA.

³  David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California 90095-1690, USA.

⁴  Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1690, USA.

Defensins are peptides that protect the host against microorganisms. Here we show that the -defensin retrocyclin 2 (RC2) inhibited influenza virus infection by blocking membrane fusion mediated by the viral hemagglutinin. RC2 was effective even after hemagglutinin attained a fusogenic conformation or had induced membrane hemifusion. RC2, a multivalent lectin, prevented hemagglutinin-mediated fusion by erecting a network of crosslinked and immobilized surface glycoproteins. RC2 also inhibited fusion mediated by Sindbis virus and baculovirus. Human -defensin 3 and mannan-binding lectin also blocked viral fusion by creating a protective barricade of immobilized surface proteins. This general mechanism might explain the broad-spectrum antiviral activity of many multivalent lectins of the innate immune system.

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