The histone H3K9 demethylase LSD1 plays a critical role in the regulation of herpes simplex virus (HSV) infection. OG-L002 is a selective inhibitor of LSD1 with an IC50 value of 0.02μM. It is also a potent inhibitor of monoamine oxidases (MAO) with IC50 values of 1.38μM and 0.72μM for MAO-A and MAO-B, respectively. OG-L002 inhibited viral immediate-early gene expression in HeLa and HFF cells with IC50 values of ~10µM and ~3µM, respectively. Treatment of Hela cells with 50µM OG-L002 for 24 hours reduced viral yields compared with the DMSO-treated controls. Also in Hela cells, pretreatment with 50µM OG-L002 for 4 hours increased the levels of total histone H3 and H3K9-me2 (20- to 30-fold) associated with viral immediate-early gene promoters. Treatment with OG-L002 (10 - 50µM) for 48 hours repressed viral reactivation in trigeminal ganglia isolated from HSV-infected mice. In BALB/c mice, pretreatment with OG-L002 (6 - 40mg/kg/day) for one week reduced the levels of detectable viral genomes in the ganglia at both 3- and 5-day post-infection. The administration of mice with OG-L002 at a dose of 20mg/kg/day reduced viral genome accumulation at 3-, 5-, and 10-day post-infection[2].
作用机制
OG-L002 is a potent LSD1 inhibitor that blocks HSV lytic replication and reactivation from latency[2].
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