論文 - 詳細
| RRC ID | 43436 |
|---|---|
| 著者 | Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T. |
| タイトル | Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. |
| ジャーナル | Antimicrob Agents Chemother |
| Abstract |
Oseltamivir (Tamiflu) and zanamivir (Relenza), two extensively used clinically effective anti-influenza drugs, are viral sialidase (also known as neuraminidase) inhibitors that prevent the release of progeny virions and thereby limit the spread of infection. Recently mortalities and neuropsychiatric events have been reported with the use of oseltamivir, especially in pediatric cases in Japan, suggesting that these drugs might also inhibit endogenous enzymes involved in sialic acid metabolism, including sialidase, sialyltransferase, and CMP-synthase, in addition to their inhibitory effects on the viral sialidase. The possible inhibition could account for some of the rare side effects of oseltamivir. However, there has been little direct evidence in regard to the sensitivities of animal sialidases to these drugs. Here, we examined whether these inhibitors might indeed affect the activities of human sialidases, which differ in primary structures and enzyme properties but possess tertiary structures similar to those of the viral enzymes. Using recombinant enzymes corresponding to the four human sialidases identified so far, we found that oseltamivir carboxylate scarcely affected the activities of any of the sialidases, even at 1 mM, while zanamivir significantly inhibited the human sialidases NEU3 and NEU2 in the micromolar range (K(i), 3.7 +/- 0.48 and 12.9 +/- 0.07 microM, respectively), providing a contrast to the low nanomolar concentrations at which these drugs block the activity of the viral sialidases. |
| 巻・号 | 52(10) |
| ページ | 3484-91 |
| 公開日 | 2008-10-1 |
| DOI | 10.1128/AAC.00344-08 |
| PII | AAC.00344-08 |
| PMID | 18694948 |
| PMC | PMC2565904 |
| MeSH | Antiviral Agents / adverse effects* Cell Line Enzyme Inhibitors / adverse effects* Humans In Vitro Techniques Kinetics Neuraminidase / antagonists & inhibitors* Neuraminidase / genetics Orthomyxoviridae / enzymology Oseltamivir / adverse effects* RNA, Messenger / genetics RNA, Messenger / metabolism Recombinant Proteins / antagonists & inhibitors Recombinant Proteins / genetics Zanamivir / adverse effects* |
| IF | 4.904 |
| 引用数 | 98 |
| WOS 分野 | PHARMACOLOGY & PHARMACY MICROBIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 42 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |