Accession Number : ADA466159


Title :   Smallpox Antiviral Drug


Descriptive Note : Final rept. 1 Jan 2003-31 Dec 2006


Corporate Author : SIGA TECHNOLOGIES INC CORVALLIS OR


Personal Author(s) : Hruby, Dennis E


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a466159.pdf


Report Date : Jan 2007


Pagination or Media Count : 56


Abstract : Using a homology-based bioinformatics approach a new structural model of the vaccinia virus (VV) I7L proteinase active site has been generated. This model was used to perform Virtual Ligand Screening of a comprehensive library of approximately 3.5 million available compounds including about 208,000 available ketones and aldehydes. Compounds with a docking score of -32 were ordered and screened using our newly developed fluorescence quench biochemical assay for those compounds able to inhibit the activity of the I7L enzyme. Compounds have been identified that inhibit I7L more than 50% at 200 pM which validate the 3D ligand binding model and provide initial leads for further rational optimization of poxvirus I7L proteinase inhibitors.


Descriptors :   *ANTIVIRAL AGENTS , *VARIOLA VIRUS , FLUORESCENCE , STRUCTURAL PROPERTIES , LIBRARIES , BIOASSAY , VACCINIA VIRUS , KETONES , ALDEHYDES , BIOCHEMISTRY , DRUGS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE