Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay.
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.
Institute of Technology, University of Tartu, Tartu, Estonia.|Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.
Mart
M
Toots
Institute of Technology, University of Tartu, Tartu, Estonia.|Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.
Mart
M
Ustav
Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.
Andres
A
Männik
Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.
Karl
K
Mumm
Institute of Chemistry, University of Tartu, Tartu, Estonia.
Kaido
K
Tämm
Institute of Technology, University of Tartu, Tartu, Estonia.
Tarmo
T
Tamm
Institute of Technology, University of Tartu, Tartu, Estonia.
Ene
0000-0002-7865-8051
E
Ustav
Institute of Technology, University of Tartu, Tartu, Estonia.|Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.|Estonian Academy of Sciences, Tallinn, Estonia.
Mart
M
Ustav
D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays / Q000379:methods*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D034741:RNA, Small Interfering; D049410:Luciferases, Renilla