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      Antiviral Drugs for EBV

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          Abstract

          Epstein–Barr virus (EBV) infects up to 95% of the adult human population, with primary infection typically occurring during childhood and usually asymptomatic. However, EBV can cause infectious mononucleosis in approximately 35–50% cases when infection occurs during adolescence and early adulthood. Epstein–Barr virus is also associated with several B-cell malignancies including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease. A number of antiviral drugs have proven to be effective inhibitors of EBV replication, yet have resulted in limited success clinically, and none of them has been approved for treatment of EBV infections.

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          Epstein-Barr virus infection and posttransplant lymphoproliferative disorder.

          M. Green, G MICHAELS (2013)
          Epstein-Barr virus (EBV) is an important pathogen in recipients of solid organ transplants (SOT). Infection with EBV manifests as a spectrum of diseases/malignancies ranging from asymptomatic viremia through infectious mononucleosis to posttransplant lymphoproliferative disorder (PTLD). EBV disease and its associated PTLD is more frequently seen when primary EBV infection occurs after transplant, a common scenario in pediatric SOT recipients. Intensity of immunosuppressive therapies also influences the risk for PTLD. The use of EBV viral load monitoring facilitates the diagnosis and management of EBV/PTLD as well as being used to inform preemptive therapy with reduction of immunosuppression, the most effective intervention for prevention of and treatment for PTLD. Other therapies, including the rituximab (anti-CD20 monoclonal antibody) and traditional chemotherapy, are also useful in the treatment of established PTLD. The future development of standards for management based on EBV viral load and routine monitoring of EBV-specific CTL responses promise further improvement in outcomes with EBV and PTLD. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
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            Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir.

            Sunwen Chou (2016)
            Mutations in the human CMV UL97 kinase gene are a major mechanism of viral resistance to two anti-CMV drugs, ganciclovir (GCV) and maribavir (MBV). GCV, the most widely used and established therapy for CMV, is a substrate for the UL97 kinase. Well-characterised GCV-resistance mutations at UL97 codons 460, 520 and 590-607 impair the phosphorylation of GCV that is necessary for its antiviral activity, presumably by altering substrate recognition. In contrast, MBV is an inhibitor of the UL97 kinase and is the first new CMV therapy to reach later stage clinical trials in many years. No MBV-resistant CMV isolates have yet been detected in clinical trials, but after culture propagation under drug, UL97 mutations that confer moderate to high-level MBV resistance have been identified at codons 353, 397, 409 and 411. These mutations are located upstream of the GCV-resistance mutations and are close to the ATP-binding and catalytic domains common to all kinases, consistent with MBV acting as a small molecule ATP-competitive kinase inhibitor. So far, no UL97 mutations are known to confer resistance to both GCV and MBV.
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              Epstein-Barr virus infections: prospects for treatment.

              S. Pagano, Joseph S Pagano (2005)
              Epstein-Barr virus (EBV) causes infectious mononucleosis and oral hairy leucoplakia, and is associated with a number of malignancies. There are, however, no regulatory agency-approved treatments for EBV-related diseases. Several antiviral drugs inhibit replication of EBV in cell culture including acyclic nucleoside and nucleotide analogues and pyrophosphate analogues, all of which inhibit the EBV DNA polymerase. Despite their potency in vitro, these drugs have limited use in vivo for treatment of acute primary EBV infection as well as EBV-associated malignancies for several reasons. Here we discuss novel anti-EBV compounds, including maribavir, potentially useful for the treatment of acute EBV infections. A number of experimental approaches for treatment of EBV-related malignancies that are not susceptible to conventional antiviral drug treatment are also discussed.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 13 June 2018
                Publication date Collection: June 2018
                Volume: 10
                Issue: 6
                Electronic Location Identifier: 197
                Affiliations
                [1 ]Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
                [2 ]Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; cbwhiteh@ 123456med.unc.edu
                [3 ]Department of Microbiology and Immunology, University of Leuven, BE-3000 Leuven, Belgium; Graciela.Andrei@ 123456rega.kuleuven.be
                Author notes
                Author information
                https://orcid.org/0000-0003-4740-2317
                Article
                Publisher ID: cancers-10-00197
                DOI: 10.3390/cancers10060197
                PMC ID: 6025560
                PubMed ID: 29899236
                SO-VID: 37564d0b-2430-4022-9c97-d1ce2a8ff90a
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 09 May 2018
                Date accepted : 12 June 2018
                Categories
                Subject: Commentary

                Keywords: epstein–barr virus,maribavir,antiviral,acyclovir,ganciclovir
                Data availability:
                Keywords: epstein–barr virus, maribavir, antiviral, acyclovir, ganciclovir

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