Premium
Comparison of inhibitor binding to feline and human immunodeficiency virus proteases: Structure‐based drug design and the resistance problem
Author(s) -
Dunn Ben M.,
Pennington Michael W.,
Frase D. Constanza,
Nash Kevin
Publication year - 1999
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1999)51:1<69::aid-bip8>3.0.co;2-#
Subject(s) - proteases , protease , virology , virus , enzyme , chemistry , protease inhibitor (pharmacology) , drug resistance , human immunodeficiency virus (hiv) , feline immunodeficiency virus , genome , binding site , lentivirus , biology , biochemistry , genetics , viral disease , viral load , gene , antiretroviral therapy
The design and synthesis of compounds targeted against human immunodeficiency virus 1 (HIV‐1) protease have resulted in effective antiviral therapies. However, the rapid replication of the virus and the inherent mutability of the viral genome result in the outgrowth of resistant strains in the majority of patients. Thus, there is a continuing need to develop new antiprotease compounds that may bind more effectively to the resistant forms of protease. This contribution examines the binding of a single inhibitor to two different retroviral proteases, HIV‐1 protease and feline immunodeficiency virus protease. Despite the overall similarity of the related retroviral enzymes, specific substitutions within the binding site cavity provide a distinctly different binding landscape that dramatically alters the affinity of compounds. Through this comparison, insights have been obtained into new strategies for drug design. New compounds based on these concepts have been tested against the two enzymes. © 1999 John Wiley & Sons, Inc. Biopoly 51: 69–77, 1999