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Article
Molecular Basis for Drug Resistance in HIV-1 Protease
Biochemistry and Molecular Pharmacology Publications and Presentations
  • Akbar Ali, University of Massachusetts Medical School
  • Rajintha M. Bandaranayake, University of Massachusetts Medical School
  • Yufeng Cai, University of Massachusetts Medical School
  • Nancy M. King, University of Massachusetts Medical School
  • Madhavi Kolli, University of Massachusetts Medical School
  • Seema Mittal, University of Massachusetts Medical School
  • Jennifer E. Foulkes-Murzycki, University of Massachusetts Medical School
  • Madhavi N. L. Nalam, University of Massachusetts Medical School
  • Ellen A. Nalivaika, University of Massachusetts Medical School
  • Aysegul Ozen, University of Massachusetts Medical School
  • Moses Prabu-Jeyabalan, University of Massachusetts Medical School
  • Kelly Thayer, University of Massachusetts Medical School
  • Celia A. Schiffer, University of Massachusetts Medical School
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Date
11-14-2010
Document Type
Article
Medical Subject Headings
Drug Resistance, Viral; HIV Antigens; HIV Protease Inhibitors; HIV-1; Humans; Virus Replication; gag Gene Products, Human Immunodeficiency Virus
Abstract
HIV-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.
Rights and Permissions
Citation: Viruses. 2010 Nov;2(11):2509-2535. Link to article on publisher's site
Comments

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 Resources
Link to Article in PubMed
PubMed ID
21994628
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Citation Information
Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, et al.. "Molecular Basis for Drug Resistance in HIV-1 Protease" Vol. 2 Iss. 11 (2010) ISSN: 1999-4915 (Linking)
Available at: http://works.bepress.com/rajintha_bandaranayake/5/