Anti-bovine viral diarrhoea virus and hepatitis C virus activity of the cyclooxygenase inhibitor SC-560.
BACKGROUND
A number of compounds were examined for their inhibitory effect on bovine viral diarrhoea virus (BVDV) replication in cell cultures and found that some cyclooxygenase (COX) inhibitors had antiviral activity against the virus.


METHODS
Determination of compounds for their anti-BVDV activity was on the basis of the inhibition of virus-induced cytopathogenicity in Mardin-Darby bovine kidney (MDBK) cells. Anti-hepatitis C virus (HCV) activity was assessed by the inhibition of viral RNA synthesis in the subgenomic HCV RNA replicon cells.


RESULTS
Among the test compounds, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) was the most active against BVDV, and its 50% effective and cytotoxic concentrations were 10.9 +/-2.8 and 93.9 +/-24.5 microM in virus and mock-infected MDBK cells, respectively. The compound also suppressed BVDV RNA synthesis in a dose-dependent fashion. Studies on the mechanism of action revealed that SC-560 did not interfere with viral entry to the host cells. Furthermore, it was assumed that the antiviral activity of SC-560 was not associated with its inhibitory effect on COX. The combination of SC-560 and interferon-alpha was additive to synergistic in inhibiting BVDV replication. More importantly, the compound proved to be a selective inhibitor of HCV replication.


CONCLUSIONS
SC-560 and its derivative might have potential as novel antiviral agents against HCV.
Okamoto
Mika
M
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Sakai
Masashi
M
Goto
Yukinori
Y
Salim
Mohammed T A
MT
Baba
Chiaki
C
Goto
Kaku
K
Watashi
Koichi
K
Shimotohno
Kunitada
K
Baba
Masanori
M
D000818:Animals; D000998:Antiviral Agents; D002417:Cattle; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000472:pathogenicity; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000998:Antiviral Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D012367:RNA, Viral; C115461:SC 560