Inhibition of human coronavirus NL63 infection at early stages of the replication cycle

Krzysztof Pyrc, Berend Jan Bosch, Ben Berkhout, Maarten F Jebbink, Ronald Dijkman, Peter Rottier, Lia van der Hoek

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.

    Original languageEnglish
    Pages (from-to)2000-8
    Number of pages9
    JournalAntimicrobial Agents and Chemotherapy
    Volume50
    Issue number6
    DOIs
    Publication statusPublished - Jun 2006

    Keywords

    • Animals
    • Antiviral Agents
    • Azauridine
    • Base Sequence
    • Cell Line
    • Cell Survival
    • Coronavirus
    • Coronavirus Infections
    • Cytidine
    • Cytopathogenic Effect, Viral
    • Humans
    • Inhibitory Concentration 50
    • Macaca mulatta
    • Molecular Structure
    • Neutralization Tests
    • Nucleosides
    • RNA Interference
    • RNA, Small Interfering
    • RNA, Viral
    • Receptors, Virus
    • Time Factors
    • Virus Replication

    Fingerprint

    Dive into the research topics of 'Inhibition of human coronavirus NL63 infection at early stages of the replication cycle'. Together they form a unique fingerprint.

    Cite this