[Colletodiol inhibits the replication of influenza A virus WSN/H1N1 by reducing the activity of viral RNA polymerase].
OBJECTIVE
To screen for compounds against influenza A virus by using the viral promoter reporter cell line HeLa-IAV-Luc and investigate their anti-viral mechanism.


METHODS
We screened the inhibitors of influenza A virus by infecting HeLa-IAV-Luc cells with influenza A virus WSN/H1N1 and treating it with the compounds isolated from microbial metabolites. The cell lysates were then subjected to the luciferase assay. We conducted the pesudovirus assay to analyze whether the compound affected the function of hemagglutinin (HA). We carried out the influenza viral promoter reporter assay to examine whether the compound could inhibitinfluenza viral RNA polymerase (vRNP) activity. The effect of anti-viral compoundon influenza viral RNA synthesis was measured by real-time fluorescence quantitative PCR.


RESULTS
Colletodiol inhibited the replication of influenza A virus in HeLa-IAV-Luc cells by luciferase assay. It did not inhibit the function of HA protein based on the results of the time-of-addition experiment and pseudovirus assay. The influenza viral polymerase promoter reporter assay indicated that Colletodiol could inhibit the activity of vRNP dramatically. Due to the inhibition of vRNP, the influenza viral RNA synthesis decreased significantly.


CONCLUSIONS
Compound Colletodiol was an inhibitor of influenza A virus. It blocks the replication of influenza A virus by reducing the activity of vRNP.
Wenbin
W
Lai
Shixiong
S
Wang
Xin
X
Ye
D000998:Antiviral Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000821:virology*; D007783:Lactones / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007783:Lactones; C111697:colletodiol; D012321:DNA-Directed RNA Polymerases