tetano
Editor, Senior Moderator
J Antibiot (Tokyo). 2019 Jan 9. doi: 10.1038/s41429-018-0134-z. [Epub ahead of print]
[h=1]Flupyranochromene, a novel inhibitor of influenza virus cap-dependent endonuclease, from Penicillium sp. f28743.[/h] Yamasaki M[SUP]1[/SUP], Igarashi M[SUP]2[/SUP], Sawa R[SUP]2[/SUP], Nosaka C[SUP]2[/SUP], Umekita M[SUP]2[/SUP], Hatano M[SUP]2[/SUP], Kimura T[SUP]2[/SUP], Iijima K[SUP]2[/SUP], Takizawa N[SUP]2[/SUP], Kato T[SUP]3[/SUP], Mizumoto K[SUP]4[/SUP], Nomoto A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 30622294 DOI: 10.1038/s41429-018-0134-z
[h=1]Flupyranochromene, a novel inhibitor of influenza virus cap-dependent endonuclease, from Penicillium sp. f28743.[/h] Yamasaki M[SUP]1[/SUP], Igarashi M[SUP]2[/SUP], Sawa R[SUP]2[/SUP], Nosaka C[SUP]2[/SUP], Umekita M[SUP]2[/SUP], Hatano M[SUP]2[/SUP], Kimura T[SUP]2[/SUP], Iijima K[SUP]2[/SUP], Takizawa N[SUP]2[/SUP], Kato T[SUP]3[/SUP], Mizumoto K[SUP]4[/SUP], Nomoto A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 30622294 DOI: 10.1038/s41429-018-0134-z