Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha - PubMed (original) (raw)

. 2004 Apr 1;189(7):1164-7.

doi: 10.1086/382597. Epub 2004 Mar 12.

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Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha

Ute Ströher et al. J Infect Dis. 2004.

Abstract

Current treatment schemes for severe acute respiratory syndrome (SARS) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)- alpha in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. Ribavirin did not inhibit viral growth at concentrations attainable in human serum. In contrast, IFN- alpha showed an in vitro inhibitory effect starting at concentrations of 1000 IU/mL. In conclusion, ribavirin alone is unlikely to be beneficial in the prophylaxis or treatment of SARS CoV infections. Clinical trials with IFN- alpha might be justified to determine a beneficial effect on the outcome of SARS.

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Figures

Figure 1.

Figure 1.

Cytopathic effect in severe acute respiratory syndrome-related coronavirus (SARS CoV)-infected Vero E6 cells. Vero E6 cells were infected with the SARS CoV at an MOI of 0.001 for 1 h and then were incubated in Dulbecco's modified Eagle's medium containing the indicated amounts of interferon-α-2b (IU/mL). Cells were fixed with 4% formalin on day 3 after infection.

Figure 2.

Figure 2.

Effect of interferon (IFN)-α-2b on virus growth. A, Reduction of virus yield in the presence of antiviral activity. Vero E6 cells were infected with ∼100 pfu of the severe acute respiratory syndrome-related coronavirus (SARS CoV). At 1 h after infection, the supernatants were replaced with Dulbecco's modified Eagle's medium (DMEM) or DMEM containing the indicated amounts of IFN-α-2b (IU/mL) for a total of 72 h. Growth of the SARS CoV isolate Tor2 was determined by plaquetitration assay from 3 independent experiments, and data are mean ± SD. B, Analysis of cell-to-cell spread of SARS CoV in the presence and absence of IFN-α-2b. Vero E6 cell monolayers were infected with 10-fold dilutions of the SARS CoV. After 1 h of virus adsorption, the inoculum was removed, and cell monolayers were overlaid with 0.9% low-meltingpoint agarose in DMEM (B2) or DMEM containing 5000 IU/mL of IFNa- 2b (B1). On day 3 after infection, cells were stained with crystal violet. C, Protein analysis. Cell lysates were subjected to 10% SDS-PAGE. Protein was electrotransferred to polyvinylidene difluoride membrane (Immobilon P membrane; Millipore). Viral antigen was detected by use of a patient serum sample and horseradish peroxidase-conjugated anti-human IgG, by use of enhanced chemiluminescence. NP, nucleoprotein. D, Comparison of the effect of antiviral activity on different SARS CoV isolates. Vero E6 cells were infected with 4 independently isolated SARS CoVs (isolates Tor2, Tor3, Tor7, and Tor684) and were analyzed for their sensitivity to IFN-α-2b, as described above.

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