Approaches for the Generation of New Anti-cytomegalovirus Agents: Identification of Protein–Protein Interaction Inhibitors and Compounds Against the HCMV IE2 Protein

  • Beatrice Mercorelli
  • Giorgio Gribaudo
  • Giorgio Palù
  • Arianna LoregianEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1119)


Human cytomegalovirus (HCMV) infection is responsible for severe, often even fatal, diseases in immunocompromised subjects and also represents the major cause of viral-associated congenital malformations in newborn children. The few drugs licensed for anti-HCMV therapy suffer from many drawbacks and none of them have been approved for the treatment of congenital infections. Furthermore, the emergence of drug-resistant viral strains represents a major concern for disease management. Thus, there is a strong need for new anti-HCMV drugs. Here we describe three different assays for the discovery of novel anti-HCMV compounds: two are in vitro assays, i.e., a fluorescence polarization (FP)-based assay and an enzyme-linked immunosorbent assay (ELISA), which are designed to search for compounds that act by disrupting the interactions between the HCMV DNA polymerase subunits, but in general can be employed to find inhibitors of any protein–protein interaction of interest; the third is a cell-based assay designed to identify inhibitors of the viral immediate-early 2 (IE2) protein activities.

Key words

Antivirals Cell-based assay DNA polymerase inhibitors Enzyme-linked immunosorbent assay Fluorescence polarization Human cytomegalovirus IE2 protein Protein–protein interaction 



The research in our laboratories was supported by MURST EX60%, Progetto di Ricerca di Ateneo 2007 (grant no. CPDA074945), and PRIN 2008 (grant no. 20085FF4J4) to A.L., by PRIN and the Piedmont Region (Ricerca Sanitaria Finalizzata) to G.G., and by Regione Veneto and Progetto Strategico di Ateneo 2008 to G.P.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Beatrice Mercorelli
    • 1
  • Giorgio Gribaudo
    • 2
  • Giorgio Palù
    • 1
  • Arianna Loregian
    • 1
    Email author
  1. 1.Department of Molecular MedicineUniversity of PaduaPaduaItaly
  2. 2.Department of Life Sciences and Systems BiologyUniversity of TurinTurinItaly

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