| 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 |
| antiviral |
| compound |
| 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/74611 |
| 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)
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