PLoS Pathogens | |
Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay | |
Karl Mumm1  Kaido Tämm1  Mart Ustav Jr.1  Tarmo Tamm1  Ene Ustav2  Mart Toots3  Andres Männik3  Mart Ustav3  | |
[1] Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia;Institute of Chemistry, University of Tartu, Tartu, Estonia;Institute of Technology, University of Tartu, Tartu, Estonia | |
关键词: DNA replication; Viral replication; Luciferase; Genomic library screening; Human papillomavirus; Human papillomavirus infection; Genomic signal processing; Viral genomics; | |
DOI : 10.1371/journal.ppat.1006168 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors. At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates for the development of antivirals against HPV and possibly against HPV-related cancers.
【 授权许可】
CC BY
【 预 览 】
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RO201902018735567ZK.pdf | 2425KB | download |