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タイトル: | iPSC screening for drug repurposing identifies anti‐RNA virus agents modulating host cell susceptibility |
著者: | Imamura, Keiko ![]() ![]() Sakurai, Yasuteru Enami, Takako Shibukawa, Ran Nishi, Yohei Ohta, Akira Shu, Tsugumine Kawaguchi, Jitsutaro Okada, Sayaka Hoenen, Thomas Yasuda, Jiro Inoue, Haruhisa ![]() ![]() ![]() |
著者名の別形: | 今村, 恵子 櫻井, 康晃 江浪, 貴子 澁川, 蘭 西, 洋平 太田, 章 川口, 実太郎 安田, 二朗 井上, 治久 |
キーワード: | Ebola virus human iPSC PPARγ SARS-CoV-2 Sendai virus SERMs |
発行日: | 6-Apr-2021 |
出版者: | Wiley |
誌名: | FEBS Open Bio |
抄録: | Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re‐emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad‐spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human‐induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti‐RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS‐CoV‐2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS‐CoV‐2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS‐CoV‐2 into host cells. These findings suggest that the identified FDA‐approved drugs can modulate host cell susceptibility against RNA viruses. |
記述: | RNAウイルスの感染を阻害する既存薬の同定 --複数の異なるRNAウイルスに対して宿主細胞の感受性を下げることにより感染を抑制する薬剤--. 京都大学プレスリリース. 2021-04-07. iPS cells in drug screenings for COVID-19. 京都大学プレスリリース. 2021-04-07. |
著作権等: | © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License (Creative Commons Attribution 4.0 International Public License), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/262587 |
DOI(出版社版): | 10.1002/2211-5463.13153 |
PubMed ID: | 33822489 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/210407-000000.html https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/210407-000000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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