論文 - 詳細
| RRC ID | 74477 |
|---|---|
| 著者 | Saito S, Funayama K, Kato W, Okuda M, Kawamoto M, Matsubara T, Sato T, Sato A, Otsuguro S, Sasaki M, Orba Y, Sawa H, Maenaka K, Shindo K, Imoto M, Arai MA. |
| タイトル | Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses. |
| ジャーナル | J Nat Prod |
| Abstract |
Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations. |
| 巻・号 | 85(11) |
| ページ | 2583-2591 |
| 公開日 | 2022-11-25 |
| DOI | 10.1021/acs.jnatprod.2c00550 |
| PMID | 36223390 |
| PMC | PMC9578650 |
| MeSH | Antiviral Agents* / chemistry Antiviral Agents* / metabolism Antiviral Agents* / pharmacology Azo Compounds* / chemistry Azo Compounds* / metabolism Azo Compounds* / pharmacology COVID-19* Chlorocebus aethiops Dogs HEK293 Cells Heat-Shock Response Humans Influenza A Virus, H1N1 Subtype* / drug effects Influenza, Human / drug therapy Madin Darby Canine Kidney Cells Orthomyxoviridae Infections / drug therapy SARS-CoV-2* / drug effects Streptomyces* / chemistry Streptomyces* / metabolism Vero Cells |
| IF | 3.782 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | MDCK(RCB0995) 293T(RCB2202) |