Introduction: The recent outbreak of severe acute respiratory syndrome (SARS) warrants the search for effective antiviral agents to treat the disease. This study describes the assessment of the antiviral potential of nitric oxide (NO) against SARS coronavirus (SARS-CoV) strain Frankfurt-1 replicating in African Green Monkey (Vero E6) cells. Results: Two organic NO donor compounds, S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP), were tested in a broad range of concentrations. The non-nitrosylated form of SNAP, N-acetylpenicillamine (NAP), was included as a control compound in the assay. Antiviral activity was estimated by the inhibition of the SARS-CoV cytopathic effect in Vero E6 cells, determined by a tetrazolium-based colorimetric method. Cytotoxicity of the compounds was tested in parallel. Conclusion: The survival rate of SARS-CoV infected cells was greatly increased by the treatment with SNAP, and the concentration of this compound needed to inhibit the viral cytopathic effect to 50% was 222 ΞΌM, with a selectivity index of 3. No anti-SARS-CoV effect could be detected for SNP and NAP. Β© 2004 International Society for Infectious Diseases. Published by Elsevier Ltd.