Discovery of HIV-1 Integrase Inhibitors

Highly active antiretroviral therapy (HAART) is the current treatment regimen for HIV/AIDS, a disease that has claimed millions worldwide. HAART is a cocktail that inhibits different stages of the viral life cycle targeting protease, reverse transcriptase, and often includes anti-fusion inhibitor enfurvitide. The addition of HIV-1 integrase (IN) inhibitor raltegravir to HAART reveals a decrease of the virus to near undetectable levels in treatment-experienced patients. Although these successes are encouraging for antiviral therapy, specific mutations resistant to raltegravir have also appeared. Drug resistant mutations is the inevitable signature of HIV with a merry-go-round history of antiviral drug development and viral evolution, highlighting the need to identify new leads for IN inhibition. Absent of a cellular