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PLoS ONE. Inhibition of Influenza H7 Hemagglutinin-Mediated Entry

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  • PLoS ONE. Inhibition of Influenza H7 Hemagglutinin-Mediated Entry

    [Source: PLoS ONE, full page: (LINK). Abstract, edited.]


    RESEARCH ARTICLE

    Inhibition of Influenza H7 Hemagglutinin-Mediated Entry

    Aleksandar Antanasijevic, Han Cheng, Duncan J. Wardrop, Lijun Rong, Michael Caffrey


    Abstract

    The recent outbreak of H7N9 influenza in China is of high concern to public health. H7 hemagglutinin (HA) plays a critical role in influenza entry and thus HA presents an attractive target for antivirals. Previous studies have suggested that the small molecule tert-butyl hydroquinone (TBHQ) inhibits the entry of influenza H3 HA by binding to the stem loop of HA and stabilizing the neutral pH conformation of HA, thereby disrupting the membrane fusion step. Based on amino acid sequence, structure and immunogenicity, H7 is a related Group 2 HA. In this work we show, using a pseudovirus entry assay, that TBHQ inhibits H7 HA-mediated entry, as well as H3 HA-mediated entry, with an IC50~6 ?M. Using NMR, we show that TBHQ binds to the H7 stem loop region. STD NMR experiments indicate that the aromatic ring of TBHQ makes extensive contact with the H7 HA surface. Limited proteolysis experiments indicate that TBHQ inhibits influenza entry by stabilizing the H7 HA neutral pH conformation. Together, this work suggests that the stem loop region of H7 HA is an attractive target for therapeutic intervention and that TBHQ, which is a widely used food preservative, is a promising lead compound.


    Citation: Antanasijevic A, Cheng H, Wardrop DJ, Rong L, Caffrey M (2013) Inhibition of Influenza H7 Hemagglutinin-Mediated Entry. PLoS ONE 8(10): e76363. doi:10.1371/journal.pone.0076363

    Editor: Luwen Zhang, University of Nebraska ? Lincoln, United States of America

    Received: July 19, 2013; Accepted: August 26, 2013; Published: October 23, 2013

    Copyright: ? 2013 Antanasijevic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Funding: The authors have no funding or support to report.

    Competing interests: The authors have declared that no competing interests exist.


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