Target intelligence / Profile preview

Replication protein E1 (Human papillomavirus type 16) (E1)

Target
E1
Molecular classification
Helicase, ATPase, Hydrolase, Isomerase, DNA-binding protein
01

Overview

The Human papillomavirus type 16 E1 protein (HPV16 E1) is a critical viral enzyme functioning as an ATP-dependent DNA 3'-5' helicase (UniProt, 2005). It is essential for the initiation and maintenance of viral DNA replication, working in coordination with the E2 protein to recognize the viral origin of replication and recruit host cell DNA polymerases (UniProt, 2008; Frontiers, 2022). HPV16 is a high-risk genotype and the primary etiological agent for cervical cancer and other anogenital and oropharyngeal malignancies (MDPI, 2024; PMC, 2022). E1's role in viral genome amplification and its potential to induce host DNA damage make it a significant factor in viral persistence and carcinogenesis (Frontiers, 2022). As a therapeutic target, E1 is being explored for the development of small-molecule inhibitors that disrupt its helicase activity or its interaction with E2 (ResearchGate, 2022; MDPI, 2024). Additionally, E1 is increasingly included in next-generation therapeutic vaccines designed to elicit robust T-cell-mediated immune responses against HPV-infected cells (PMC, 2023). The protein's high conservation across HPV types makes it an attractive target for broad-spectrum antiviral development (Taylor & Francis, 2022). However, the integration of the viral genome into the host DNA in advanced cancers often leads to the loss of E1 expression, presenting a challenge for targeting in late-stage disease (Frontiers, 2022). Current research focuses on identifying potent inhibitors through in silico screening and drug repurposing campaigns (Taylor & Francis, 2022).

Other names
ATP-dependent helicase E1DNA 3'-5' helicase E1VE1_HPV16Replication protein E1
02

Mechanism of action

Inhibition of E1-E2 protein-protein interaction, inhibition of E1 helicase activity, and induction of E1-specific T-cell immune responses.

03

Biological functions

Viral DNA replicationDNA unwindingInitiation of viral DNA replicationRecruitment of host DNA polymerase
04

Disease associations

Cervical cancerHPV infectionOropharyngeal cancerAnogenital cancer
05

Safety considerations

Host DNA damage (double-strand breaks)Off-target effects on host helicasesViral genome integration leading to E1 loss in late-stage cancer
06

Interacting drugs

Indandione-containing inhibitors

4 more in the full profile.

07

Biomarkers

HPV16 E1 mRNAHPV16 E1C RNA

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