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Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication.
Tsukamoto, Yuta; Hiono, Takahiro; Yamada, Shintaro; Matsuno, Keita; Faist, Aileen; Claff, Tobias; Hou, Jianyu; Namasivayam, Vigneshwaran; Vom Hemdt, Anja; Sugimoto, Satoko; Ng, Jin Ying; Christensen, Maria H; Tesfamariam, Yonas M; Wolter, Steven; Juranek, Stefan; Zillinger, Thomas; Bauer, Stefan; Hirokawa, Takatsugu; Schmidt, Florian I; Kochs, Georg; Shimojima, Masayuki; Huang, Yi-Shuian; Pichlmair, Andreas; Kümmerer, Beate M; Sakoda, Yoshihiro; Schlee, Martin; Brunotte, Linda; Müller, Christa E; Igarashi, Manabu; Kato, Hiroki.
Affiliation
  • Tsukamoto Y; Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Hiono T; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.
  • Yamada S; Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
  • Matsuno K; Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Faist A; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.
  • Claff T; Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.
  • Hou J; One Health Research Center, Hokkaido University, Sapporo, Hokkaido, Japan.
  • Namasivayam V; Institute of Virology Muenster, Westfaelische Wilhelms-University, Muenster, Germany.
  • Vom Hemdt A; CiM-IMPRS, Westfaelische Wilhelms-University Muenster, International Max Planck Research School - Molecular Biomedicine, Muenster, Germany.
  • Sugimoto S; PharmaCenter Bonn and Pharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
  • Ng JY; PharmaCenter Bonn and Pharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
  • Christensen MH; PharmaCenter Bonn and Pharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
  • Tesfamariam YM; Institute of Virology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Wolter S; Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
  • Juranek S; Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Zillinger T; Institute of Innate Immunity, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Bauer S; Institute of Innate Immunity, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Hirokawa T; Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University Hospital Bonn, Bonn, Germany.
  • Schmidt FI; Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Kochs G; Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University Hospital Bonn, Bonn, Germany.
  • Shimojima M; Institute of Immunology, Philipps-University Marburg, Marburg, Germany.
  • Huang YS; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Pichlmair A; Institute of Immunology, Philipps-University Marburg, Marburg, Germany.
  • Kümmerer BM; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan.
  • Sakoda Y; Division of Biomedical Science, University of Tsukuba, Tsukuba, Japan.
  • Schlee M; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
  • Brunotte L; Institute of Innate Immunity, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Müller CE; Core Facility Nanobodies, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Igarashi M; Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • Kato H; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Science ; 379(6632): 586-591, 2023 02 10.
Article in En | MEDLINE | ID: mdl-36758070
ABSTRACT
Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces, called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / Biological Products / RNA Caps / Tubercidin / Alphainfluenzavirus / Betainfluenzavirus / Enzyme Inhibitors / Methyltransferases Limits: Animals / Humans Language: En Journal: Science Year: 2023 Document type: Article Affiliation country: Germany
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / Biological Products / RNA Caps / Tubercidin / Alphainfluenzavirus / Betainfluenzavirus / Enzyme Inhibitors / Methyltransferases Limits: Animals / Humans Language: En Journal: Science Year: 2023 Document type: Article Affiliation country: Germany