Flupyranochromene, a novel inhibitor of influenza virus cap-dependent endonuclease, from Penicillium sp. f28743
| Autor: | Ryuichi Sawa, Kiyoko Iijima, Taira Kato, Akio Nomoto, Masayuki Igarashi, Masaki Hatano, Chisato Nosaka, Maya Umekita, Kiyohisa Mizumoto, Naoki Takizawa, Manabu Yamasaki, Tomoyuki Kimura |
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| Rok vydání: | 2019 |
| Předmět: |
Microbiological Techniques
0301 basic medicine Protein subunit 030106 microbiology medicine.disease_cause Antiviral Agents Biochemistry 01 natural sciences Virus Viral Proteins 03 medical and health sciences Endonuclease Influenza A Virus H1N1 Subtype Drug Discovery Influenza A virus medicine Enzyme Inhibitors Polymerase Pharmacology chemistry.chemical_classification biology 010405 organic chemistry Chemistry Penicillium RNA RNA-Dependent RNA Polymerase Molecular biology In vitro 0104 chemical sciences Enzyme Fermentation biology.protein |
| Zdroj: | The Journal of Antibiotics. 72:125-133 |
| ISSN: | 1881-1469 0021-8820 |
| Popis: | Influenza virus RNA polymerase has cap-dependent endonuclease activity that produces capped RNA fragments for priming viral mRNA synthesis. This enzymatic activity is essential for viral propagation, but it is not present in any host cellular enzyme, making it an attractive target for the development of anti-influenza drugs. Here, we isolated a novel inhibitor of cap-dependent endonuclease, named flupyranochromene, from the fermentation broth of the fungus Penicillium sp. f28743. Structural analysis revealed that this compound bears a putative pharmacophore that chelates divalent metal ion(s) present in the endonuclease active site in the PA subunit of the polymerase. Consistently, in vitro endonuclease assays showed that flupyranochromene exerts its inhibitory effects by blocking endonucleolytic cleavage by the PA subunit of viral RNA polymerase complex. |
| Databáze: | OpenAIRE |
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