Fragment screening and HIV therapeutics

Top Curr Chem. 2012;317:181-200. doi: 10.1007/128_2011_232.


Fragment screening has proven to be a powerful alternative to traditional methods for drug discovery. Biophysical methods, such as X-ray crystallography, NMR spectroscopy, and surface plasmon resonance, are used to screen a diverse library of small molecule compounds. Although compounds identified via this approach have relatively weak affinity, they provide a good platform for lead development and are highly efficient binders with respect to their size. Fragment screening has been utilized for a wide range of targets, including HIV-1 proteins. Here, we review the fragment screening studies targeting HIV-1 proteins using X-ray crystallography or surface plasmon resonance. These studies have successfully detected binding of novel fragments to either previously established or new sites on HIV-1 protease and reverse transcriptase. In addition, fragment screening against HIV-1 reverse transcriptase has been used as a tool to better understand the complex nature of ligand binding to a flexible target.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / therapeutic use*
  • Crystallography, X-Ray
  • Drug Discovery*
  • HIV / drug effects*
  • HIV / enzymology
  • HIV Infections / drug therapy*
  • HIV Protease / metabolism
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Surface Plasmon Resonance


  • Anti-HIV Agents
  • Small Molecule Libraries
  • HIV Reverse Transcriptase
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1