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Review
. 2024 Jan 15;16(1):124.
doi: 10.3390/v16010124.

Update of Natural Products and Their Derivatives Targeting Epstein-Barr Infection

Rosamaria Pennisi  1 , Paola Trischitta  1   2 , Marianna Costa  1   2 , Assunta Venuti  3 , Maria Pia Tamburello  1 , Maria Teresa Sciortino  1
Affiliations
Review

Update of Natural Products and Their Derivatives Targeting Epstein-Barr Infection

Rosamaria Pennisi et al. Viruses. .

Abstract

Epstein-Barr (EBV) is a human γ-herpesvirus that undergoes both a productive (lytic) cycle and a non-productive (latent) phase. The virus establishes enduring latent infection in B lymphocytes and productive infection in the oral mucosal epithelium. Like other herpesviruses, EBV expresses its genes in a coordinated pattern during acute infection. Unlike others, it replicates its DNA during latency to maintain the viral genome in an expanding pool of B lymphocytes, which are stimulated to divide upon infection. The reactivation from the latent state is associated with a productive gene expression pattern mediated by virus-encoded transcriptional activators BZLF-1 and BRLF-1. EBV is a highly transforming virus that contributes to the development of human lymphomas. Though viral vectors and mRNA platforms have been used to develop an EBV prophylactic vaccine, currently, there are no vaccines or antiviral drugs for the prophylaxis or treatment of EBV infection and EBV-associated cancers. Natural products and bioactive compounds are widely studied for their antiviral potential and capability to modulate intracellular signaling pathways. This review was intended to collect information on plant-derived products showing their antiviral activity against EBV and evaluate their feasibility as an alternative or adjuvant therapy against EBV infections and correlated oncogenesis in humans.

Keywords: Epstein–Barr virus; human oncogenic virus; natural antivirals.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
EBV infection and antiviral treatment. (1) Entry of EBV into the oropharyngeal epithelium mediated by the interaction between integrins on cell membranes and BMRF2 viral glycoprotein. (2) The infection of naïve B cells by the interaction of specific receptors on the B cell surface (CD21/CD35) with glycoproteins (gp350/220) on the viral surface. This interaction is a key step in the viral entry process and sets the stage for subsequent events in the viral life cycle within the host cell. (3) Activation of intracellular signals such as apoptosis, cell proliferation, and angiogenesis following naïve B-cell infection. (4) LCLs expressing nuclear proteins (EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C and EBNA-LP), membrane proteins (LMP-1, LMP-2A and LMP-2B), small RNAs (EBER1 and EBER2) and transcripts (BARTs). (5) The expression of BZLF1 is crucial to switch from latent to lytic infection. In red, antiviral drugs currently in use against EBV target several mechanisms.
Figure 2
Figure 2
Natural compounds targeting viral proteins or intracellular pathways triggered by EBV.
See this image and copyright information in PMC

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