1. Abstract 2015
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects 50 to 80% of the adults
in the USA and over 90% worldwide. Although clinical symptoms are rare in healthy
immunocompetent individuals, HCMV causes severe disease such as blindness, hepatitis and
encephalitis in immunocompromised individuals such as AIDS patients, organ transplant
recipients and neonates. Clinical manifestations of the disease may occur due to primary
infection as well as reactivation of the virus from a latent state. No vaccines against HCMV have
been approved for clinical use, and the available antiviral drugs suffer from efficacy, resistance
and toxicity issues. The aim of the current study is to design and optimize a fluorescence-based
screening assay to discover new drugs from NIH Clinical Collection (NCC) Library that can
inhibit HCMV infection. The clinically tested compounds in the NIH Clinical Collection Library
are highly drug-like with known safety profiles. After discovering potential compounds (drugs),
further dilutions were made to discover the EC50 that is the concentration of the drug that gives
half maximal response. In the experiment, a total of 72 compounds were screened. Consequently,
only two compounds were identified as potential hits based on significant reduction in virus
encoded GFP fluorescence. Cells were stained with Hoechst to calculate the total number of cells
present versus cells showing GFP positive expression. Further studies are necessary to determine
the mechanism of action of the drugs and the stage of virus replication block.