Journal Article

Pyridine <i>N</i>-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

Jan Balzarini, Els Keyaerts, Leen Vijgen, Frank Vandermeer, Miguel Stevens, Erik De Clercq, Herman Egberink and Marc Van Ranst

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 3, pages 472-481
Published in print March 2006 | ISSN: 0305-7453
Published online December 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki481
Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

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Objectives: Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture.

Methods: FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis.

Results and conclusions: A wide variety of pyridine N-oxide derivatives have been found to be inhibitory against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in CRFK and simian kidney (Vero) cell cultures, respectively. The oxide part on the pyridine moiety proved indispensable for anti-coronavirus activity. The potency and virus specificity of the pyridine N-oxide derivatives varied depending the nature and specific location of substituents (i.e. alkyl, halogeno, nitro, etc.) on the different parts of the molecule. The most selective compounds were active in the higher microgram per litre range, being non-toxic at 50–100 mg/L. There was a poor structure-antiviral activity relationship (SAR) for the pyridine N-oxide derivatives against Fe-CoV and SARS-CoV. One of the most active and selective compounds was shown to inhibit Fe-CoV replication at the transcriptional level.

Keywords: severe acute respiratory syndrome; feline coronavirus; FIPV

Journal Article.  3768 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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