gms | German Medical Science

Severe acute respiratory syndrome (SARS) has recently emerged as a new severe human disease, resulting globally in 774 deaths from 8098 reported probable cases. A novel member of the Coronaviridae family has been identified as the causative agent of this pulmonary disease. Although the initial global outbreak of SARS appears to have been successfully contained, SARS will remain a serious concern while there continues to be no suitable vaccine or effective drug treatment. This study describes the assessment of the in vitro antiviral potential of nitric oxide (NO) against SARS coronavirus (SARS-CoV). 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 also included 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. 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 CPE to 50% was 222,3 µM with a selectivity index of 3. No anti-SARS-CoV effect could be detected for SNP or NAP. NO is a key molecule in the pathogenesis of infectious diseases. In a variety of microbial infections NO biosynthesis occurs particularly through the expression of an inducible nitric oxide synthase (iNOS). This molecule has been reported to have antiviral effects in a variety of DNA and RNA viruses, including mouse hepatitis virus, a murine coronavirus. Recently, replication of SARS-CoV was shown to be inhibited by glycyrrhizin, an active compound of liquorice roots. Glycyrrhizin upregulates the expression of iNOS and production of NO in macrophages. This provides additional evidence that NO and NO-inducers may have an antiviral effect against the SARS-CoV.