Importance of the field: Epstein–Barr virus (EBV) is a ubiquitous human
herpesvirus that is causally associated with endemic forms of Burkitt’s lymphoma,
nasopharyngeal carcinoma and lymphoproliferative disease in immunosuppressed
individuals. On a global scale, EBV infects > 90% of the adult
population and is responsible for ~ 1% of all human cancers. To date, there
is no efficacious drug or therapy for the treatment of EBV infection and
EBV-related diseases.
Areas covered in this review: In this review, we discuss the existing anti-
EBV inhibitors and those under development. We discuss the value of different
molecular targets, including EBV lytic DNA replication enzymes as well
as proteins that are expressed exclusively during latent infection, such as
EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1. As the
atomic structure of the EBNA-1 DNA binding domain has been described, it
is an attractive target for in silico methods of drug design and small molecule
screening. We discuss the use of computational methods that can greatly
facilitate the development of novel inhibitors and how in silico screening
methods can be applied to target proteins with known structures, such as
EBNA-1, to treat EBV infection and disease.
What the reader will gain: The reader is familiarized with the problems in
targeting of EBV for inhibition by small molecules and how computational
methods can greatly facilitate this process.
Take home message: Despite the impressive efficacy of nucleoside analogs for
the treatment of herpesvirus lytic infection, there remain few effective treatments
for latent infections. As EBV latent infection persists within and contributes
to the formation of EBV-associated cancers, targeting EBV latent
proteins is an unmet medical need. High-throughput in silico screening can
accelerate the process of drug discovery for novel and selective agents that
inhibit EBV latent infection and associated disease.