Delving into the Latest Updates on Trifluoromethyl-tubercidin with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

CMTR1 x PB2

Mechanism

CMTR1 modulators(cap methyltransferase 1 modulators), PB2 inhibitors(polymerase basic protein 2 (PB2) inhibitors)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Influenza A virus infection

Inactive Indication-

Originator Organization

University of Bonn

Active Organization

University of Bonn

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Schlee, Martin ; Huang, Yi-Shuian ; Hiono, Takahiro ; Kato, Hiroki ; Vom Hemdt, Anja ; Brunotte, Linda ; Bauer, Stefan ; Sugimoto, Satoko ; Juranek, Stefan ; Zillinger, Thomas ; Faist, Aileen ; Matsuno, Keita ; Hirokawa, Takatsugu ; Hou, Jianyu ; Tesfamariam, Yonas M ; Kochs, Georg ; Kümmerer, Beate M ; Yamada, Shintaro ; Claff, Tobias ; Christensen, Maria H ; Ng, Jin Ying ; Igarashi, Manabu ; Shimojima, Masayuki ; Pichlmair, Andreas ; Wolter, Steven ; Namasivayam, Vigneshwaran ; Tsukamoto, Yuta ; Müller, Christa E ; Schmidt, Florian I ; Sakoda, Yoshihiro

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.

100 Deals associated with Trifluoromethyl-tubercidin

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