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 microg/ml and 16 microg/ml, respectively, and the IC50 of ribavirin for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849 was 20 microg/ml and 80 microg/ml, while the 50% cytotoxic concentration of mizoribine and ribavirin for Vero E6 cells exceeded 200 microg/ml. In a yield reduction assay, mizoribine (10 microg/ml) and ribavirin (40 microg/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 up to 100 microg/ml.
Saijo
Masayuki
M
Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. msaijo@nih.go.jp
Morikawa
Shigeru
S
Fukushi
Shuetsu
S
Mizutani
Tetsuya
T
Hasegawa
Hideki
H
Nagata
Noriyo
N
Iwata
Naoko
N
Kurane
Ichiro
I
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D012254:Ribavirin / Q000737:chemistry / Q000494:pharmacology*; D012263:Ribonucleosides / Q000737:chemistry / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012263:Ribonucleosides; D012254:Ribavirin; C010052:mizoribine