GPC-N114 inhibits picornavirus replication.

<p>(A) Structural formula of GPC-N114. (B) Representative dose-response curves of multicycle CPE-reduction assays for CVB3, PV1, and EV71. CPE was quantified by MTS assay at 3 d p.i. and is expressed as percentage of uninfected, untreated controls. (C, D) Antiviral activity of GPC-N114 against CVB3 and EMCV. BGM cells were infected with CVB3 (left panels) or EMCV (right panels) at an MOI of 0.1. Immediately after infection, GPC-N114 was added at the indicated concentrations (C) or at 10 μM (D). The enterovirus inhibitor guanidine hydrochloride (GuHCl) and the cardiovirus inhibitor dipyridamole were included as controls. Virus titers were determined by endpoint titration after 8 h (C) or at the indicated times p.i. (D). Experiments were performed in triplicate and mean values ± SD are depicted. (E) Antiviral activity of GPC-N114 against a range of picornaviruses. Cells were infected with the indicated viruses at an MOI of 0.5 after which 10 μM GPC-N114 was added. Virus titers were determined at 8 h p.i. Experiments were performed in triplicate and mean values ± SD are depicted. (F) GPC-N114 inhibits viral RNA replication. RNA of subgenomic replicons of CVB3 or EMCV was transfected into BGM cells. Subsequently, cells were treated either with 0.1% DMSO, 10 μM GPC-N114, 2 mM GuHCl, or 80 μM dipyridamole. Firefly luciferase levels were determined 2, 4, 6, and 8 h after RNA transfection to assess the level of replication and translation. Experiments were performed in triplicate and mean values ± SD are depicted.