Development of a novel screening platform for the identification of small molecule inhibitors of human adenovirus

Antiviral Effects of Curcumin on Adenovirus Replication

“…An effective method used to discover novel antiviral compounds is to screen libraries of small molecules to assess their effect on viral replication. Several groups have performed such high throughput screens (HTS) to identify compounds affecting HAdV [ 6 , 14 , 15 , 16 , 17 ]. Using reporter viruses derived from several HAdV types and expressing green fluorescent protein (GFP), Sanchez-Cespedes et al [ 14 ] identified the piperazinone derivative 15D8 as an effective inhibitor of HAdV replication.…”

“…Our research group developed an HTS protocol to identify compounds that inhibit HAdV replication [ 16 ]. We utilized a HAdV type 5-based construct that expressed red fluorescent protein (RFP) as part of the late transcription unit, such that RFP is only expressed at appreciable levels following viral DNA replication [ 19 ].…”

“…We utilized a HAdV type 5-based construct that expressed red fluorescent protein (RFP) as part of the late transcription unit, such that RFP is only expressed at appreciable levels following viral DNA replication [ 19 ]. As such, the degree to which a test compound affects viral gene expression and replication inversely correlates with quantity of RFP present in the treated cells [ 16 ]. Using this HTS strategy, we tested the Prestwick library (~1200 compounds, most of which are FDA-approved) for compounds affecting HAdV infection and identified 11 compounds with anti-HAdV activity [ 16 ].…”

“…As such, the degree to which a test compound affects viral gene expression and replication inversely correlates with quantity of RFP present in the treated cells [ 16 ]. Using this HTS strategy, we tested the Prestwick library (~1200 compounds, most of which are FDA-approved) for compounds affecting HAdV infection and identified 11 compounds with anti-HAdV activity [ 16 ]. Follow-up studies on three cardiotonic steroids (digoxin, digitoxigenin, and lanatoside C) identified in this screen showed that these compounds primarily affected early 1 A (E1A) expression, and ultimately all reduced virus yield from treated cells [ 16 ].…”

“…Using this HTS strategy, we tested the Prestwick library (~1200 compounds, most of which are FDA-approved) for compounds affecting HAdV infection and identified 11 compounds with anti-HAdV activity [ 16 ]. Follow-up studies on three cardiotonic steroids (digoxin, digitoxigenin, and lanatoside C) identified in this screen showed that these compounds primarily affected early 1 A (E1A) expression, and ultimately all reduced virus yield from treated cells [ 16 ]. We also screened the Cayman Epigenetic Screening library, containing 150 small molecules that modulate the activity of epigenetic regulatory proteins, including methyltransferases, demethylases, histone acetyltransferases and deacetylases, and acetylated lysine readers, and identified 19 compounds exhibiting anti-HAdV activity [ 17 ].…”