Anti-Bovine Viral Diarrhoea Virus Activity of Novel Diphenylmethane Derivatives

• Published in: Antiviral chemistry & chemotherapy Vol. 20; no. 5; pp. 193 - 200
• Main Authors: Salim, Mohammed TA, Okamoto, Mika, Hosoda, Shinnosuke, Aoyama, Hiroshi, Hashimoto, Yuichi, Baba, Masanori
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2010; Sage Publications Ltd
• Subjects: Antigens, Viral - metabolism; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Benzhydryl Compounds - chemistry; Benzhydryl Compounds - pharmacology; Cell culture; Cell Line; Cytotoxicity; Diarrhea; Diarrhea Viruses, Bovine Viral - drug effects; Diarrhea Viruses, Bovine Viral - metabolism; Diarrhea Viruses, Bovine Viral - physiology; Dose-Response Relationship, Drug; Hepatitis C; Replication; Reverse transcription; RNA, Viral - biosynthesis; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.3851/IMP1528

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 μM. They were not cytotoxic at concentrations up to 100 μM. 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.