Article
Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs
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Published: | May 26, 2004 |
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The aim of this study is to investigate whether a panel of commercially available antiviral drugs exhibit in-vitro anti SARS-CoV activity. A drug screening assay that scores for SARS-CoV-induced cytopathic effects on cultured cells was used. These experiments allow for the rapid screening of commercially available antiviral agents, enabling those with in vitro evidence of activity to move expeditiously into clinical studies due to the already available safety and pharmacokinetic information in humans for other disease indications. Tested were nineteen clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. A cell-based assay utilizing cytopathic endpoints (CPE) was set up using SARS-CoV infection of Vero E6 cells to screen these antiviral compounds. The initial screen was followed by a plaque reduction assay to determine the EC50 of compounds showing positive results in the primary assay. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, beta-1b, alpha-n1 and alpha-n3. Ribavirin, a drug widely used in initial efforts to manage SARS infections, did not demonstrate antiviral activity in our assays at clinically useful doses. These findings support clinical testing of approved interferons for the treatment of SARS.