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The viral genomic origin-of-replication DNA is a specific nucleotide sequence within a viral genome where the process of DNA replication is initiated (Wikipedia) [6]. It serves as a recruitment site for viral and host replication proteins, including initiator proteins, helicases, and polymerases, which assemble into a replisome to duplicate the viral genetic material (PMC) [3]. In many viruses, such as Herpes Simplex Virus (HSV) and Human Papillomavirus (HPV), the origin contains conserved motifs and AT-rich regions that facilitate DNA unwinding (Nucleic Acids Research) [19]. As a therapeutic target, the origin of replication is highly attractive because its disruption can selectively halt viral proliferation without affecting host cell genomic stability (Taylor & Francis) [15]. Current research focuses on using decoy oligonucleotides, CRISPR/Cas9 gene editing, and sequence-specific minor groove binders to block protein-DNA interactions or physically disrupt the origin sequence (PMC) [16]. While most approved antivirals target viral enzymes like polymerases, targeting the origin DNA offers a strategy to overcome drug resistance and achieve long-term viral suppression (ASM Journals) [18].
Inhibition of protein-DNA binding, DNA sequence disruption, and structural stabilization of the origin duplex.
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