Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

Shun Saito, Kayo Funayama, Wataru Kato, Mayu Okuda, Meiko Kawamoto, Teruhiko Matsubara, Toshinori Sato, Akihiko Sato, Satoko Otsuguro, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Katsumi Maenaka, Kazutoshi Shindo, Masaya Imoto, Midori A. Arai

研究成果: Article査読

抄録

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 IC50values 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 IC50values (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 IC50concentrations.

本文言語English
ページ(範囲)2583-2591
ページ数9
ジャーナルJournal of Natural Products
85
11
DOI
出版ステータスPublished - 2022 11月 25

ASJC Scopus subject areas

  • 分析化学
  • 分子医療
  • 薬理学
  • 薬科学
  • 創薬
  • 補完代替医療
  • 有機化学

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