Anti-bovine viral diarrhoea virus activity of novel diphenylmethane derivatives.
BACKGROUND
A number of compounds were examined for their inhibitory effects on bovine viral diarrhoea virus (BVDV), a surrogate model of hepatitis C virus, in cell cultures. Among them, some diphenylmethane derivatives were found to be selective inhibitors of BVDV.


METHODS
Determination of compounds for their anti-BVDV activity was based on the inhibition of virus-induced cytopathic effect in Madin-Darby bovine kidney cells and reduction of infectious virus particles in culture supernatants. To gain insight into the mechanism of action, the inhibition of viral entry and RNA synthesis in the host cells was also determined by real-time reverse transcription-PCR.


RESULTS
Among the test compounds, four diphenylmethane derivatives significantly inhibited BVDV replication with a 50% effective concentration ranging between 6.3 and 10.8 muM. They were not cytotoxic at concentrations up to 100 muM. The representative compound, SH-595A, reduced the virus titre of culture supernatants in a dose-dependent manner. In addition, the compound appeared to somewhat affect viral entry to the host cells. Although SH-595A was inhibitory to viral RNA synthesis, the inhibition was achieved only at high concentrations and was not comparable to its antiviral activity.


CONCLUSIONS
The novel diphenylmethane derivatives are effective against BVDV replication and might have a unique mechanism of action.
Salim
Mohammed T A
MT
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Okamoto
Mika
M
Hosoda
Shinnosuke
S
Aoyama
Hiroshi
H
Hashimoto
Yuichi
Y
Baba
Masanori
M
D000956:Antigens, Viral / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D012367:RNA, Viral / Q000096:biosynthesis; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D001559:Benzhydryl Compounds; D012367:RNA, Viral; C010129:diphenylmethane