title: Inhibition of human coronavirus NL63 infection at early stages of the replication cycle.
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.
authors.affiliation: Department of Human Retrovirology, University of Amsterdam, The Netherlands. k.a.pyrc@amc.uva.nl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pyrc
authors.forename: Berend Jan
authors.initials: BJ
authors.lastname: Bosch
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Maarten F
authors.initials: MF
authors.lastname: Jebbink
authors.forename: Ronald
authors.initials: R
authors.lastname: Dijkman
authors.forename: Peter
authors.initials: P
authors.lastname: Rottier
authors.forename: Lia
authors.initials: L
authors.lastname: van der Hoek
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001380:Azauridine / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017934:Coronavirus / Q000737:chemistry / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D018352:Coronavirus Infections / Q000188:drug therapy / Q000821:virology*; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D015394:Molecular Structure; D009500:Neutralization Tests; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects; D011991:Receptors, Virus / Q000378:metabolism; D013997:Time Factors; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011991:Receptors, Virus; D003562:Cytidine; D001380:Azauridine; C010737:N(4)-hydroxycytidine