Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound

Els Keyaerts, Leen Vijgen, Luni Chen, Piet Maes, Göran Hedenstierna, Marc Van Ranst, Els Keyaerts, Leen Vijgen, Luni Chen, Piet Maes, Göran Hedenstierna, Marc Van Ranst

Abstract

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 microM, with a selectivity index of 3. No anti-SARS-CoV effect could be detected for SNP and NAP.

Figures

Figure 1
Figure 1
(A) Increased survival rate of SARS FFM-1 infected Vero E6 cells by the treatment of SNAP. Optical density at 492 nm of mitochondrial activity was measured. Data are expressed as means±S.D. (B) Percent protection achieved by the compounds in SARS-CoV infected cells is calculated as follows: 100 × [(ODvirus + compound − ODsvirus control)/(ODcell control − ODsvirus control)]/(ODcompound control/ODcell control). Bars indicate SD.

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