Antiviral activity of favipiravir (T-705) against mammalian and avian bornaviruses

Bornaviruses, non-segmented, negative-strand RNA viruses, are emerging agents with the potential for causing various types of neurological symptoms. Previous studies have shown that ribavirin, a nucleic acid analog with broad-spectrum antiviral activity, has a potent antiviral effect on infections w...

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Vydáno v:	Antiviral research Ročník 143; s. 237 - 245
Hlavní autoři:	Tokunaga, Tomoya, Yamamoto, Yusuke, Sakai, Madoka, Tomonaga, Keizo, Honda, Tomoyuki
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 01.07.2017
Témata:	Amides - administration & dosage Amides - pharmacology Animals Antiviral Agents - administration & dosage Antiviral Agents - pharmacology Avian bornavirus Bird Diseases - virology Borna Disease - drug therapy Borna Disease - virology Borna disease virus Borna disease virus - genetics Bornaviridae - drug effects Bornaviridae - genetics Cell Line Cercopithecus aethiops Favipiravir Microbial Sensitivity Tests Pyrazines - administration & dosage Pyrazines - pharmacology Quail Replication RNA, Viral - analysis Time Factors Vero Cells Viral Load - drug effects Virus Replication - drug effects Replication Avian bornavirus Borna disease virus Favipiravir
ISSN:	0166-3542, 1872-9096, 1872-9096
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Bornaviruses, non-segmented, negative-strand RNA viruses, are emerging agents with the potential for causing various types of neurological symptoms. Previous studies have shown that ribavirin, a nucleic acid analog with broad-spectrum antiviral activity, has a potent antiviral effect on infections with a mammalian bornavirus, Borna disease virus (BoDV-1), as well as avian bornaviruses. However, ribavirin-based treatment does not eliminate bornaviruses from persistently infected cells and viral replication resumes after treatment cessation. Therefore, the development of a novel effective anti-bornavirus treatment is needed. To identify such agents, we screened nucleoside/nucleotide mimetics for agents with anti-bornavirus activity. We used Vero cells infected with recombinant BoDV-1 carrying Gaussia luciferase to monitor BoDV-1 replication and found that favipiravir (T-705) is a potent inhibitor of BoDV-1 replication. T-705 suppressed BoDV-1 replication in a dose- and time-dependent manner during the observation period of 4 weeks. Notably, no increase in luciferase activity or in the number of BoDV-1-positive cells was detected in the at least 4 weeks following T-705 removal. Finally, we demonstrated that T-705 effectively suppressed viral replication of both BoDV-1 and an avian bornavirus, suggesting that T-705 may have a strong antiviral activity against a broad range of bornaviruses. Our findings provide a novel and effective option for treating persistent bornavirus infection. •We established a novel Vero cells infected with recombinant BoDV-1 carrying Gaussia luciferase to monitor BoDV-1 replication.•T-705 suppressed BoDV-1 replication in a dose- and time-dependent manner.•T-705 reduced BoDV-1 load to an almost undetectable level at 28 days of treatment.•T-705 is a candidate antiviral against a broad range of bornaviruses.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-3542 1872-9096 1872-9096
DOI:	10.1016/j.antiviral.2017.04.018