論文 - 詳細
| RRC ID | 75682 |
|---|---|
| 著者 | Tsukamoto Y, Hiono T, Yamada S, Matsuno K, Faist A, Claff T, Hou J, Namasivayam V, Vom Hemdt A, Sugimoto S, Ng JY, Christensen MH, Tesfamariam YM, Wolter S, Juranek S, Zillinger T, Bauer S, Hirokawa T, Schmidt FI, Kochs G, Shimojima M, Huang YS, Pichlmair A, Kümmerer BM, Sakoda Y, Schlee M, Brunotte L, Müller CE, Igarashi M, Kato H. |
| タイトル | Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication. |
| ジャーナル | Science |
| 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. |
| 巻・号 | 379(6632) |
| ページ | 586-591 |
| 公開日 | 2023-2-10 |
| DOI | 10.1126/science.add0875 |
| PMID | 36758070 |
| MeSH | A549 Cells Animals Antiviral Agents* / chemistry Antiviral Agents* / pharmacology Biological Products* / chemistry Biological Products* / pharmacology Computer Simulation Enzyme Inhibitors* / chemistry Enzyme Inhibitors* / pharmacology Humans Influenzavirus A* / drug effects Influenzavirus B* / drug effects Methyltransferases* / antagonists & inhibitors Mice RNA Caps* / metabolism RNA, Messenger / metabolism RNA, Viral / biosynthesis Streptomyces / chemistry Tubercidin* / analogs & derivatives Tubercidin* / pharmacology Virus Replication* / drug effects |
| IF | 41.846 |
| リソース情報 | |
| ヒト病原ウイルス | |