Identification of human adenovirus replication inhibitors from a library of small molecules targeting cellular epigenetic regulators

Saha, Bratati; Parks, Robin J.

Human adenovirus (HAdV) can cause severe disease in certain at-risk populations such as newborns, the elderly and those with compromised immune systems. Unfortunately, no FDA-approved anti-HAdV drug is currently available for treatment. Within the nucleus of infected cells, the HAdV genome associates with histones and forms a chromatin-like structure during early infection, and viral gene expression appears regulated by cellular epigenetic processes. Thus, one potential therapeutic strategy to combat HAdV disease may be to target the cellular proteins involved in modifying the viral nucleoprotein structure and facilitating HAdV gene expression and replication. We have screened a panel of small molecules that modulate the activity of epigenetic regulatory proteins for compounds affecting HAdV gene expression. Several of the compounds, specifically chaetocin, gemcitabine and lestaurtinib, reduced HAdV recovery by 100- to 1000-fold, while showing limited effect on cell health, suggesting that these compounds may indeed be promising as anti-HAdV therapeutics.