Table 1

Therapeutic inhibitors of EBV reactivation and replication

Inhibitor of EBV reactivation Mechanism of action References
Anti-herpesvirus drugs
 AciclovirAciclovir triphosphate is a specific inhibitor of herpesvirus DNA polymerase leading to obligate chain termination. 74
 Ganciclovir/valganciclovirPreferential inhibitor of herpesvirus DNA polymerase and competitive inhibitor of dGTP incorporation into DNA. 75
 Omaciclovir (H2G)/valomaciclovirH2G triphosphate is a specific inhibitor of herpesvirus DNA polymerase leading to limited chain elongation. 76
 MaribavirOral benzimidazole L-riboside which inhibits HCMV and EBV protein kinases. 77
 CidofovirCidofovir diphosphate selectively inhibits viral DNA polymerase. 78–80
Other drugs
 CimetidineH2 antagonist, inhibition of T suppressor cells, cellular proliferation, adhesion and angiogenesis. 81–85
 ZidovudineThymidine analogue which selectively inhibits HIV reverse transcriptase. Anti-EBV effect not proven nor elucidated. 86–88 90
 ClevudineClevudine triphosphate inhibits multiple steps in the intracellular life cycle of hepatitis B virus. Anti-EBV effect not proven nor elucidated. 86–89
 ValpromidePrevention of expression of immediate-early EBV genes, BZLF1 and BRLF1. 91
 JQ1, and bromodomain and extraterminalJQ1 inhibits the growth of EBV+ nasopharyngeal cancer cells; proapoptotic, antiproliferative and enhancement of radiological sensitivity. 92 93
 ArtesunateInhibition of immediate-early EBV protein synthesis. 94 95
 H31 sequence-specific inhibitorInhibition of EBNA1-dependent OriP sequence-specific DNA-binding activity. 96 97
 EBI2 inhibitor, GSK682753AInhibition of oxysterol-induced EBI2 activation, β-arrestin recruitment and chemotaxis in B lymphocytes. 98 99
 EBI2 inhibitor, NIBR189EBI2 inhibition; blocks migration in U937 monocytes. 100
Vitamins
 Vitamin CInhibition of EBV activation in human lymphoblastoid cells. Killing of EBV+ Burkitt lymphoma cells and EBV-transformed cells in vitro. 101–103
 Vitamin DDirect inhibition of enveloped viruses. Upregulation of antimicrobial peptides LL-37 and human β-defensin. LL-37 may disrupt viral envelope. 104–109
 Retinoic acidNegative regulator of EBV BZLF1 and thus inhibits EBV lytic cycle. Irreversible inhibition of EBV-transformed B lymphocytes. 110–113
Dietary constituents and supplements
 ResveratrolInhibition of EBV lytic cycle through effects on multiple molecular targets. 114–116
 LuteolinInhibition of promoter activity of EBV immediate-early genes, BRLF1 and BZLF1. Reduces genomic instability and suppresses tumourigenicity of EBV. 117–124
 ApigeninInhibition of EBV BRLF1 and BZLF1 activity. 125
 Astragalus extractInhibition of expression of BZLF1, BRLF1 and EA-D during EBV lytic cycle. 126
 Epigallocatechin-3-gallateDownregulation of LMP1. Inhibition of EBV-induced B-lymphocyte transformation via suppression of RelA acetylation. 127–131
 Delta-9-tetrahydrocannabinol (THC)THC inhibits replication of γ-herpesviruses. Mechanism not understood. 132
 L-arginineSuppression of EBV replication through enhancement of iNOS and nitric oxide. 133
 SulforaphaneInhibition of transactivation of Rta, but not Zta. 134
 CurcuminEnhanced apoptosis-mediated inhibition of proliferation of EBV-transformed lymphoblastoid cell line. Inhibition of BZLF1 transcription. 135–137
 BaicaleinInhibition of EBV+ NPC through repression of activity of EBNA1 Q-promoter. 138
 (+)-RutamarinCellular topoisomerase II catalytic inhibitor. 139 140

  • EAD, early antigen D; EBI2, EBV-induced 2 gene; EBNA1, EBV nuclear antigen 1; EBV, Epstein-Barr virus; HCMV, human cytomegalovirus; NPC, nasopharyngeal carcinoma; iNOS, inducible nitric oxide synthase.