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

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 RNAI (siRNA1), siRNA2, beta-D-N-4-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 mu g/ml, 2 mu M, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (> 10 mg/ml, > 40 mu M, > 200 nM, > 200 nM, > 100 mu M, and 80 mu M, respectively). These agents may be investigated further for the treatment of coronavirus infections.