Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication

• DOI: 10.1126/science.add0875
• Publication Date: 2023-03-31T19:58:57Z
• Authors: Yuta Tsukamoto; Takahiro Hiono; Shintaro Yamada; Keita Matsuno; Aileen Faist; Tobias Claff; Jianyu Hou; Vigneshwaran Nama...; Anja vom Hemdt; Satoko Sugimoto; Jin Ying Ng; Maria H. Christensen; Yonas M. Tesfamariam; Steven Wolter; Stefan Juranek; Thomas Zillinger; Stefan Bauer; Takatsugu Hirokawa; Florian I. Schmidt; Georg Kochs; Masayuki Shimojima; Yi-Shuian Huang; Andreas Pichlmair; Beate M. Kümmerer; Yoshihiro Sakoda; Martin Schlee; Linda Brunotte; Christa E. Müller; Manabu Igarashi; Hiroki Kato
• Keywords: Transcription

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 by 2'-O-ribose methyltransferase 1 (MTr1) is essential for initiation influenza A B virus replication, but not other cap-snatching viruses. identified with silico compound screening functional analysis derivative natural product from Streptomyces, trifluoromethyl-tubercidin (TFMT), inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket restrict replication. Mechanistically, TFMT impairs association viral polymerase basic protein 2 subunit human lung explants vivo mice. acts synergistically approved anti-influenza drugs.