Title:Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges
Volume: 19
Issue: 18
Author(s): Chandrashekhar Voshavar*
Affiliation:
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307,United States
Keywords:
Acquired immunodeficiency syndrome, Human immunodeficiency virus, Protease inhibitors, Antiretroviral drugs,
Drug discovery, AIDS therapy.
Abstract: Acquired Immunodeficiency Syndrome (AIDS) is a chronic disease characterized by multiple
life-threatening illnesses caused by a retro-virus, Human Immunodeficiency Virus (HIV). HIV infection
slowly destroys the immune system and increases the risk of various other infections and diseases. Although,
there is no immediate cure for HIV infection/AIDS, several drugs targeting various cruxes of
HIV infection are used to slow down the progress of the disease and to boost the immune system. One of
the key therapeutic strategies is Highly Active Antiretroviral Therapy (HAART) or ' AIDS cocktail' in a
general sense, which is a customized combination of anti-retroviral drugs designed to combat the HIV
infection. Since HAART’s inception in 1995, this treatment was found to be effective in improving the
life expectancy of HIV patients over two decades. Among various classes of HAART treatment regimen,
Protease Inhibitors (PIs) are known to be widely used as a major component and found to be effective in
treating HIV infection/AIDS. For the past several years, a variety of protease inhibitors have been reported.
This review outlines the drug design strategies of PIs, chemical and pharmacological characteristics
of some mechanism-based inhibitors, summarizes the recent developments in small molecule based
drug discovery with HIV protease as a drug target. Further discussed are the pharmacology, PI drug resistance
on HIV PR, adverse effects of HIV PIs and challenges/impediments in the successful application of
HIV PIs as an important class of drugs in HAART regimen for the effective treatment of AIDS.