A new study published in the Proceedings of the National Academy of Sciences (USA) has identified 15 compounds that are potent against the severe acute respiratory syndrome virus (SARS-CoV) in cell-based assays, including two drugs that are currently in use and several that are already in the clinical development pipeline.

The only available therapy for SARS-CoV is a combination of ribavirin and corticosteroids, which is effective — but only at concentrations that produce severe side effects. Since SARS was first isolated in 2002, it has caused more than 700 deaths worldwide, so finding effective antivirals for SARS is a priority.

High-throughput screening requires a simple and reliable assay system. Wu et al. used a cell-based assay to screen more than 10,000 compounds, all administered at 10 μM, for inhibition of virus cytopathic effects. From this primary screen, 50 compounds were selected for further analysis, first to determine if the compounds were cytotoxic and second to measure the concentration of the compound required to inhibit virus replication by 50% (EC50).

The most potent inhibitor was valinomycin, a peptide insecticide with an EC50 of 0.85 μM. Aescin and reserpine, already in use in Europe and the United States, respectively, were also active against SARS-CoV, but neither drug is currently prescribed as an antiviral. Compounds that are structurally similar to reserpine and aescin were also screened, resulting in 10 new anti-SARS active compounds. Finally, a potent inhibitor of the HIV protease, TL-3, which is being developed as a treatment for AIDS in cats, was also effective against the SARS protease. These studies offer new hope for rapidly available SARS therapeutics.