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Ribavirin-related compounds exert in vitro inhibitory effects toward rabies virus.

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Title: Ribavirin-related compounds exert in vitro inhibitory effects toward rabies virus.
Authors: Anindita, Paulina D Browse this author
Sasaki, Michihito Browse this author →KAKEN DB
Okada, Kazuma Browse this author
Ito, Naoto Browse this author
Sugiyama, Makoto Browse this author
Saito-Tarashima, Noriko Browse this author
Minakawa, Noriaki Browse this author
Shuto, Satoshi Browse this author →KAKEN DB
Otsuguro, Satoko Browse this author
Ichikawa, Satoshi Browse this author →KAKEN DB
Matsuda, Akira Browse this author →KAKEN DB
Maenaka, Katsumi Browse this author →KAKEN DB
Orba, Yasuko Browse this author →KAKEN DB
Sawa, Hirofumi Browse this author →KAKEN DB
Keywords: rabies virus
nucleoside analog
Issue Date: Jun-2018
Publisher: Elsevier
Journal Title: Antiviral research
Volume: 154
Start Page: 1
End Page: 9
Publisher DOI: 10.1016/j.antiviral.2018.03.011
PMID: 29601893
Abstract: Rabies remains an invariably fatal neurological disease despite the availability of a preventive vaccination and post-exposure prophylaxis that must be immediately administered to the exposed individual before symptom onset. There is no effective medication for treatment during the symptomatic phase. Ribavirin, a guanine nucleoside analog, is a potent inhibitor of rabies virus (RABV) replication in vitro but lacks clinical efficacy. Therefore, we attempted to identify potential ribavirin analogs with comparable or superior anti-RABV activity. Antiviral activity and cytotoxicity of the compounds were initially examined in human neuroblastoma cells. Among the tested compounds, two exhibited a 5- to 27-fold higher anti-RABV activity than ribavirin. Examination of the anti-RABV mechanisms of action of the compounds using time-of-addition and minigenome assays revealed that they inhibited viral genome replication and transcription. Addition of exogenous guanosine to RABV-infected cells diminished the antiviral activity of the compounds, suggesting that they are involved in guanosine triphosphate (GTP) pool depletion by inhibiting inosine monophosphate dehydrogenase (IMPDH). Taken together, our findings underline the potency of nucleoside analogs as a class of antiviral compounds for the development of novel agents against RABV.
Rights: ©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐々木 道仁

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