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Antimicrobial Agents and Chemotherapy, June 2006, p. 2000-2008, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.01598-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of Human Coronavirus NL63 Infection at Early Stages of the Replication Cycle

Krzysztof Pyrc,1* Berend Jan Bosch,2 Ben Berkhout,1 Maarten F. Jebbink,1 Ronald Dijkman,1 Peter Rottier,2 and Lia van der Hoek1*

Department of Human Retrovirology, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands,1 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands2

Received 16 December 2005/ Returned for modification 28 February 2006/ Accepted 20 March 2006

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, ß-D-N4-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.

* Corresponding author. Mailing address: Department of Human Retrovirology, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: 31 20 566 75 10. Fax: 31 20 691 65 31. E-mail for Krzysztof Pyrc: k.a.pyrc{at}amc.uva.nl. E-mail for Lia van der Hoek: c.m.vanderhoek{at}amc.uva.nl.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2000-2008, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.01598-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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