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Evaluation of Broad Anti-Coronavirus Activity of Autophagy-Related Compounds Using Human Airway Organoids.
Hashimoto, Rina; Tamura, Tomokazu; Watanabe, Yukio; Sakamoto, Ayaka; Yasuhara, Naoko; Ito, Hayato; Nakano, Masahiro; Fuse, Hiromitsu; Ohta, Akira; Noda, Takeshi; Matsumura, Yasufumi; Nagao, Miki; Yamamoto, Takuya; Fukuhara, Takasuke; Takayama, Kazuo.
Afiliación
  • Hashimoto R; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Tamura T; Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
  • Watanabe Y; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Sakamoto A; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Yasuhara N; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Ito H; Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
  • Nakano M; Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
  • Fuse H; Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
  • Ohta A; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Noda T; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
  • Matsumura Y; Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
  • Nagao M; Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
  • Yamamoto T; Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
  • Fukuhara T; Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
  • Takayama K; Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
Mol Pharm ; 20(4): 2276-2287, 2023 04 03.
Article en En | MEDLINE | ID: mdl-36946991
To deal with the broad spectrum of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that threaten human health, it is essential to not only drugs develop that target viral proteins but also consider drugs that target host proteins/cellular processes to protect them from being hijacked for viral infection and replication. To this end, it has been reported that autophagy is deeply involved in coronavirus infection. In this study, we used airway organoids to screen a chemical library of autophagic modulators to identify compounds that could potentially be used to fight against infections by a broad range of coronaviruses. Among the 80 autophagy-related compounds tested, cycloheximide and thapsigargin reduced SARS-CoV-2 infection efficiency in a dose-dependent manner. Cycloheximide treatment reduced the infection efficiency of not only six SARS-CoV-2 variants but also human coronavirus (HCoV)-229E and HCoV-OC43. Cycloheximide treatment also reversed viral infection-induced innate immune responses. However, even low-dose (1 µM) cycloheximide treatment altered the expression profile of ribosomal RNAs; thus, side effects such as inhibition of protein synthesis in host cells must be considered. These results suggest that cycloheximide has broad-spectrum anti-coronavirus activity in vitro and warrants further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus Humano 229E / COVID-19 Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus Humano 229E / COVID-19 Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos