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Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral

Dipon Das1, Nathan W Smith1, Xu Wang1

  • 1VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA.

Virology
|June 2, 2017
PubMed

Insights

The drug calcein blocks human papillomavirus (HPV) DNA replication by disrupting essential protein interactions. This finding suggests calcein as a potential therapeutic for HPV infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Human papillomaviruses (HPV) cause diseases like cancer, with no direct antivirals targeting their life cycle.
  • The cellular protein TopBP1 interacts with HPV16 E2, crucial for viral DNA replication.
  • Current treatments only manage HPV disease symptoms, not the virus itself.

Purpose of the Study:

  • To investigate if the drug calcein can inhibit HPV16 DNA replication.
  • To determine if calcein's effect on HPV replication is specific and occurs at non-toxic levels.

Main Methods:

  • Studying the interaction between HPV16 E2 and TopBP1.
  • Assessing calcein's impact on HPV16 E1-E2 DNA replication in vitro.
  • Evaluating calcein's effect on E2-mediated transcription.

Main Results:

  • Calcein effectively blocks HPV16 E1-E2 DNA replication at the origin of replication.
  • The drug functions at non-toxic concentrations.
  • Calcein specifically inhibits replication without affecting E2's transcriptional regulation.

Conclusions:

  • Calcein disrupts the formation of the viral replication complex.
  • Calcein demonstrates potential as a novel antiviral therapeutic agent against HPV.
  • Calcein or its derivatives could be developed for treating HPV-induced diseases.
Keywords:
AntiviralCalceinChromatin immunoprecipitationE2 and E1Human papillomavirusReplicationTopBP1Transcription

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