Figure 3.

Antiviral activity is independent of OGG1 inhibition. (A) Correlation between compounds’ inhibition of HAZV primary infection and OGG1 activity. Antiviral activity was measured on primary infection in the HAZV phenotypic antiviral assay and IC₅₀ of hOGG1-inhibition was determined by an in vitro OGG1 activity assay. Correlations were determined using the Bravais–Pearson correlation coefficient. Chemical structures of TH4448, TH3289 and TH6744. (B–D) U2OS cells were reverse transfected with two individual siRNAs targeting OGG1 mRNA for 48 h, followed by infection with HAZV for 24 h. Percentage of HAZV-positive cells (B) and nuclei count (C) at 24 hpi. Data are expressed as mean ± SD of n = 2 biological replicates and statistical significance was determined by using one-way ANOVA with Dunnett’s multiple comparison analysis. (D) Representative Western blot image of OGG1 protein levels upon OGG1 siRNA depletion after 72 h. (E–G) U2OS cells were reverse transfected with four pooled siRNAs targeting OGG1 for 48 h, followed by infection with HAZV (MOI 1) for 24 h. Percentage of HAZV-positive cells (E), titer in Vero cells (F) and cell viability (G) were quantified at 24 hpi. Data are expressed as mean ± SD of n = 3 biological replicates. Statistical significance was determined by using one-way ANOVA with Dunnett’s multiple comparison analysis.