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Selective Targeting of Virus Replication by Proton Pump Inhibitors.

Susan M Watanabe1, Lorna S Ehrlich1, Madeleine Strickland2

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|March 6, 2020
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Summary
This summary is machine-generated.

Proton pump inhibitors like tenatoprazole show potential as broad-spectrum antivirals by inhibiting viral budding. Their efficacy depends on intracellular activation, paving the way for new antiviral therapies.

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Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Proton pump inhibitors (PPIs) tenatoprazole and esomeprazole inhibit HIV-1 egress by blocking Tsg101-ubiquitin interaction.
  • The ESCRT-I complex is crucial for enveloped virus budding and release.

Purpose of the Study:

  • To investigate the antiviral potential of tenatoprazole against a broader range of viruses.
  • To explore the structure-activity relationship between prazole chemistry, prodrug activation, and HIV-1 inhibition.

Main Methods:

  • Testing tenatoprazole's efficacy against enveloped (Filoviridae, Alphavirus, Herpesviridae) and non-enveloped (Poliovirus) viruses.
  • Assessing the correlation between in vitro prodrug activation rates and antiviral activity in cell-based assays.

Main Results:

  • Tenatoprazole inhibited replication of Filoviridae, Alphavirus, and Herpesviridae families but not Flaviviruses or Poliovirus.
  • Prazole prodrugs require intracellular activation, and their in vitro activation rate correlates with cellular efficacy.

Conclusions:

  • Tenatoprazole exhibits broad-spectrum antiviral activity against certain enveloped viruses.
  • Intracellular activation is critical for prazole-based antiviral efficacy, suggesting a mechanism for drug repurposing.