tetano
Editor, Senior Moderator
J Nat Prod. 2018 Dec 5. doi: 10.1021/acs.jnatprod.8b00656. [Epub ahead of print]
[h=1]Spirostaphylotrichin X from a Marine-Derived Fungus as an Anti-influenza Agent Targeting RNA Polymerase PB2.[/h] Wang J[SUP]1,[/SUP][SUP]2[/SUP], Chen F[SUP]3[/SUP], Liu Y[SUP]1[/SUP], Liu Y[SUP]1[/SUP], Li K[SUP]1[/SUP], Yang X[SUP]4[/SUP], Liu S[SUP]3,[/SUP][SUP]5[/SUP], Zhou X[SUP]1,[/SUP][SUP]5[/SUP], Yang J[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A new spirocyclic γ-lactam, named spirostaphylotrichin X (1), and three related known spirostaphylotrichins (2-4) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures were determined by spectroscopic analyses. Spirostaphylotrichin X (1) displayed obvious inhibitory activities against multiple influenza virus strains, with IC[SUB]50[/SUB] values from 1.2 to 5.5 μM. Investigation of the mechanism showed that 1 inhibited viral polymerase activity and interfered with the production of progeny viral RNA. Homogeneous time-resolved fluorescence, surface plasmon resonance assays, and a molecular docking study revealed that 1 could inhibit polymerase PB2 protein activity by binding to the highly conserved region of the cap-binding domain of PB2. These results suggest that 1 inhibits the replication of influenza A virus by interfering with the activity of PB2 protein and that 1 represents a new type of potential lead compound for the development of anti-influenza therapeutics.
PMID: 30516983 DOI: 10.1021/acs.jnatprod.8b00656
[h=1]Spirostaphylotrichin X from a Marine-Derived Fungus as an Anti-influenza Agent Targeting RNA Polymerase PB2.[/h] Wang J[SUP]1,[/SUP][SUP]2[/SUP], Chen F[SUP]3[/SUP], Liu Y[SUP]1[/SUP], Liu Y[SUP]1[/SUP], Li K[SUP]1[/SUP], Yang X[SUP]4[/SUP], Liu S[SUP]3,[/SUP][SUP]5[/SUP], Zhou X[SUP]1,[/SUP][SUP]5[/SUP], Yang J[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A new spirocyclic γ-lactam, named spirostaphylotrichin X (1), and three related known spirostaphylotrichins (2-4) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures were determined by spectroscopic analyses. Spirostaphylotrichin X (1) displayed obvious inhibitory activities against multiple influenza virus strains, with IC[SUB]50[/SUB] values from 1.2 to 5.5 μM. Investigation of the mechanism showed that 1 inhibited viral polymerase activity and interfered with the production of progeny viral RNA. Homogeneous time-resolved fluorescence, surface plasmon resonance assays, and a molecular docking study revealed that 1 could inhibit polymerase PB2 protein activity by binding to the highly conserved region of the cap-binding domain of PB2. These results suggest that 1 inhibits the replication of influenza A virus by interfering with the activity of PB2 protein and that 1 represents a new type of potential lead compound for the development of anti-influenza therapeutics.
PMID: 30516983 DOI: 10.1021/acs.jnatprod.8b00656