Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus

The activity of inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors, mizoribine and ribavirin, against severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was determined by plaque reduction and yield reduction assays. Mizoribine and ribavirin selectively inhibited replication of SARS-CoV. The 50% inhibitory concentration (IC50) of mizoribine for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, as determined by plaque reduction was 3.5 mu g/ml and 16 mu g/ml, respectively, and the IC50 of ribavirin for SARS-CoV Frankfurt- I and SARS-CoV HKU39849 was 20 mu g/ml and 80 mu g/ml, while the 50% cytotoxic concentration of mizoribine and ribavirin for Vero E6 cells exceeded 200 mu g/ml. In a yield reduction assay, mizoribine (10 mu g/ml) and ribavirin (40 mu g/ml) inhibited the replication of SARS-CoV and reduced the infectious SARS-CoV titers to one-tenth or less. Mizoribine inhibited replication of SARS-CoV more strongly than ribavirin. However, neither drug could completely inhibit replication of SARS-CoV even at concentrations Lip to 100 mu g/ml. (c) 2005 Elsevier B.V. All rights reserved.