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Epstein-Barr virus nuclear antigen 1 (EBNA1) is a multifunctional viral protein essential for the persistence, replication, and maintenance of the Epstein-Barr virus (EBV) episome within host cells (UniProt P03211). It functions as a sequence-specific DNA-binding protein that attaches the viral genome to host chromosomes during mitosis, ensuring the viral DNA is partitioned into daughter cells (PMID: 31533975). Beyond its role in genome maintenance, EBNA1 acts as a transcriptional regulator for other latent viral genes and contributes to immune evasion through its Gly-Ala repeat domain, which inhibits its own proteasomal degradation and subsequent MHC class I presentation (PMID: 15107843). EBNA1 is expressed in all EBV-associated malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin lymphoma, making it an attractive therapeutic target (PMID: 33441435). Current drug development efforts, such as the small molecule VK-2019, focus on disrupting EBNA1's DNA-binding or dimerization domains to eliminate the viral reservoir and inhibit tumor growth (ClinicalTrials.gov NCT03682315). Additionally, EBNA1 has been strongly linked to the pathogenesis of multiple sclerosis through molecular mimicry with host proteins, further expanding its clinical relevance as a target for intervention (PMID: 35025605).
Inhibition of EBNA1 DNA binding and dimerization to prevent viral genome maintenance and transcription.
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