Affiliation:
1. Department of Human Retrovirology, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
2. Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands
Abstract
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, β-
d
-N
4
-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 μg/ml, 2 μM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 μM, >200 nM, >200 nM, >100 μM, and 80 μM, respectively). These agents may be investigated further for the treatment of coronavirus infections.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology