Cell-permeable artificial zinc-finger proteins as potent antiviral drugs for human papillomaviruses

Takashi Mino, Tomoaki Mori, Yasuhiro Aoyama, Takashi Sera

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Human papillomavirus (HPV) is one of the important pharmaceutical targets because infection of the high-risk types causes invasive cervical cancer. However, effective antiviral drugs for HPV have not been developed so far. In the present study, we constructed cell-permeable artificial zinc-finger proteins (AZPs) by fusing an AZP previously generated for inhibition of HPV-18 DNA replication with a cell-penetrating peptide (CPP) as candidates for new antiviral drugs against HPV. We confirmed that these CPP-AZP fusions reduced the replication rate in transient replication assays when added to the culture medium. In particular, 250 nM CPP-AZP (designated AZP-R9) containing a 9-mer of arginine as the CPP reduced HPV-18 DNA replication to 3% of that of a control, and the 50% effective concentration (EC50) was <31 nM. Furthermore, a cytotoxicity assay revealed that the 50% inhibitory concentration (IC50) of AZP-R9 was >10 μM. Therefore, the selectivity index, defined as IC50/EC50, was >300, which is better than that of the antiviral cidofovir for HPVs. Thus, our results demonstrate that cell-permeable AZPs could serve as potent protein-based antiviral drugs.

Original languageEnglish
Pages (from-to)1291-1298
Number of pages8
JournalArchives of Virology
Volume153
Issue number7
DOIs
Publication statusPublished - Jul 1 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Virology

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