Influenza replication is significanlty reduced when PLD2 is inhibited by either VU034739 (3) or ML395 (6l). A549 cells were pretreated with either DMSO or 10 μM VU0364739 or 10 μM ML395 (7l) for 1 hour, then infected with either: A. 1 MOI H1N1 influenza B. 1 MOI H3N2 influenza C. 1 MOI H5N1 influenza D. 1 MOI H7N9 influenza. After 24 hours post-infection, the infectious supernatant containing the virus was removed and titrated on MDCK cells to assess viral production. Under PLD2 inhibitor treatment, poor viral replication was observed in all influenza strains tested by 24 hours post-infection, and the viral output defect was noted as early as 12 hours post-infection in the case of H3N2 and H7N9. Differences were assessed using a two-way ANOVA and Bonferroni’s post-test, where * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.