論文 - 詳細
| RRC ID | 52118 |
|---|---|
| 著者 | Wada Y, Orba Y, Sasaki M, Kobayashi S, Carr MJ, Nobori H, Sato A, Hall WW, Sawa H. |
| タイトル | Discovery of a novel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus. |
| ジャーナル | Virology |
| Abstract |
Chikungunya fever (CHIKF) is caused by chikungunya virus (CHIKV) infection which is a re-emerging mosquito-borne zoonosis. At present, there are no approved therapeutics for CHIKF. Herein, we have investigated candidate compounds which can inhibit CHIKV infection. Screening of chemical compound libraries were performed and one candidate, a benzimidazole-related compound designated Compound-A was found to inhibit infection by several CHIKV strains and a Sindbis virus strain at nanomolar concentrations. To investigate the inhibitory mechanism of action, a Compound-A resistant CHIKV (res-CHIKV) was isolated and a key mutation associated with resistance was identified by reverse-genetic recombinant CHIKVs containing amino acid substitutions present in res-CHIKV. These results demonstrated that the target site of Compound-A was the M2295 residue in the nonstructural protein 4 (nsP4), which is located in one of the functional domains of RNA-dependent RNA-polymerase (RdRp). We also confirmed that Compound-A inhibits RdRp function of CHIKV by using CHIKV replicons. |
| 巻・号 | 505 |
| ページ | 102-112 |
| 公開日 | 2017-5-1 |
| DOI | 10.1016/j.virol.2017.02.014 |
| PII | S0042-6822(17)30055-7 |
| PMID | 28236746 |
| MeSH | Amino Acid Sequence Amino Acid Substitution / genetics Animals Antiviral Agents / pharmacology* Base Sequence Benzimidazoles / pharmacology* Chikungunya Fever / drug therapy Chikungunya Fever / virology Chikungunya virus / drug effects* Chikungunya virus / genetics Chlorocebus aethiops Drug Resistance, Viral / genetics* HEK293 Cells Humans RNA-Dependent RNA Polymerase / antagonists & inhibitors* RNA-Dependent RNA Polymerase / genetics Sequence Alignment Sequence Analysis, RNA Vero Cells Viral Nonstructural Proteins / antagonists & inhibitors* Viral Nonstructural Proteins / genetics Virus Replication / drug effects |
| IF | 2.819 |
| 引用数 | 14 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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) |