Bandaranayake, Rajintha M.
King, Nancy M.
Foulkes-Murzycki, Jennifer E.
Nalam, Madhavi N. L.
Nalivaika, Ellen A.
Schiffer, Celia A.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
KeywordsDrug Resistance, Viral
HIV Protease Inhibitors
gag Gene Products, Human Immunodeficiency Virus
Immunology and Infectious Disease
MetadataShow full item record
AbstractHIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease's function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.
SourceViruses. 2010 Nov;2(11):2509-2535. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/26006
Co-author Aysegul Ozen is a student in the Biochemistry & Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related ResourcesLink to Article in PubMed