Technology ID

Anti-Viral Compounds that Inhibit HIV Activity

Lead Inventor
Beutler, John (NCI)
Jiang, Jian-kang (NCATS)
Chung, Suhman (NCI)
Thomas, Craig (NCATS)
LeGrice, Stuart (NCI)
Wilson, Jennifer (NCI)
Therapeutic Areas
Infectious Disease
Development Stages
Lead IC

Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity.  Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2.  Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells.  The toxicity thought to be a result of inhibition of multiple essential mammalian metalloenzymes.  We reasoned that the potential beneficial application of tropolone RNase H inhibition might be of therapeutic use if the toxic effects in mammalian cell were eliminated.  By selectively adding steric bulk to add new drug-enzyme contacts for the RNase H active site, a number of novel compounds, that have initially demonstrated reduced cytotoxicity, have been produced.  Importantly, these novel compounds appear to retain antiviral activity essential for use as therapeutics.

Competitive Advantages:

  • Potentially reduced toxicity
  • Availability of x-ray crystallographic information to guide analog design

Commercial Applications:

  • As an HIV-1 therapeutic
Licensing Contact:
Hastings, Whitney