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Inhibition of adenovirus replication by a trisubstituted piperazin-2-one derivative

Javier Sanchez-Cespedes1, Crystal L Moyer1, Landon R Whitby2

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Road, Mailcode IMM4, La Jolla, CA 92037, USA.

Antiviral Research
|June 8, 2014
PubMed

Insights

Researchers identified a novel compound, 15D8, that effectively inhibits adenovirus (Ad) DNA replication. This discovery offers a promising new antiviral strategy for disseminated Ad infections, particularly in immunocompromised patients.

Area of Science:

  • Virology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Disseminated adenovirus (Ad) infections are increasing, especially in immunocompromised individuals like transplant recipients.
  • High morbidity and mortality are associated with Ad infections in these vulnerable populations.
  • There are currently no approved Ad-specific antiviral drugs available for clinical use.

Purpose of the Study:

  • To identify novel small molecule compounds that can inhibit adenovirus infection.
  • To find potential therapeutic candidates for treating disseminated Ad infections.

Main Methods:

  • High-throughput screening (HTS) of over 25,000 synthetic small molecule libraries.
  • Antiviral activity and cytotoxicity assays were performed on identified compounds.
  • Mechanism of action studies focused on viral DNA replication.

Main Results:

  • A trisubstituted piperazin-2-one derivative, designated 15D8, was identified as a potent inhibitor of Ad infection.
  • Compound 15D8 demonstrated significant antiviral activity at low micromolar concentrations with minimal cytotoxicity.
  • 15D8 was found to selectively inhibit Ad DNA replication within the host cell nucleus.

Conclusions:

  • Compound 15D8 represents a promising lead for the development of a new class of antiviral agents against adenovirus.
  • This compound has the potential to address the unmet medical need for effective treatments against disseminated Ad infections.

Keywords:
AdenovirusAntiviral compoundDNA replication inhibitor

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