Next Article in Journal
Mind the Gap: How Some Viruses Infect Their Hosts
Next Article in Special Issue
Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C
Previous Article in Journal
Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs
Review

Molecular Basis for Drug Resistance in HIV-1 Protease

1
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
2
Department of Pediatrics, University of Rochester, Rochester, NY 14627, USA
3
Division of Basic Sciences, The Commonwealth Medical College, 150 N. Washington Avenue, Scranton, PA 18503, USA
*
Author to whom correspondence should be addressed.
Viruses 2010, 2(11), 2509-2535; https://doi.org/10.3390/v2112509
Received: 8 October 2010 / Revised: 22 October 2010 / Accepted: 28 October 2010 / Published: 12 November 2010
(This article belongs to the Special Issue HIV Drug Resistance 2010)
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.
Keywords: drug resistance; HIV-1 protease; protease inhibitors; substrate envelope; structure based drug design drug resistance; HIV-1 protease; protease inhibitors; substrate envelope; structure based drug design
MDPI and ACS Style

Ali, A.; Bandaranayake, R.M.; Cai, Y.; King, N.M.; Kolli, M.; Mittal, S.; Murzycki, J.F.; Nalam, M.N.L.; Nalivaika, E.A.; Özen, A.; Prabu-Jeyabalan, M.M.; Thayer, K.; Schiffer, C.A. Molecular Basis for Drug Resistance in HIV-1 Protease. Viruses 2010, 2, 2509-2535. https://doi.org/10.3390/v2112509

AMA Style

Ali A, Bandaranayake RM, Cai Y, King NM, Kolli M, Mittal S, Murzycki JF, Nalam MNL, Nalivaika EA, Özen A, Prabu-Jeyabalan MM, Thayer K, Schiffer CA. Molecular Basis for Drug Resistance in HIV-1 Protease. Viruses. 2010; 2(11):2509-2535. https://doi.org/10.3390/v2112509

Chicago/Turabian Style

Ali, Akbar, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer F. Murzycki, Madhavi N.L. Nalam, Ellen A. Nalivaika, Ayşegül Özen, Moses M. Prabu-Jeyabalan, Kelly Thayer, and Celia A. Schiffer 2010. "Molecular Basis for Drug Resistance in HIV-1 Protease" Viruses 2, no. 11: 2509-2535. https://doi.org/10.3390/v2112509

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop