HIV Protease Inhibitors (PIs) have become one of the most effective anti-viral drugs on the market. Darunavir (DRV), the most potent FDA-approved PI, has been essential in the fight against HIV/AIDS. However, the ability of the HIV protease to mutate and grow resistance has become a global concern. To address this issue, two new series of PIs were designed using the substrate envelope hypothesis. UMass 1-10 and the mono-/di-hydroxyl series compounds are derived from the DRV backbone, with modifications made on the P1' and P2' sites. The compounds were kinetically tested against resistant mutants and crystal structures were solved. Pico-molar potencies were observed for all compounds. These results can be used to design new PIs with increased efficacy against a wide range of mutants.

• This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

Creator

• Kosovrasti, Klajdi
• Henes, Mina

Publisher

• Worcester Polytechnic Institute

Identifier

• E-project-040718-205918

Advisor

• Heilman, Destin
• Mattson, Anita Elaine

Year

• 2018

Sponsor

• UMass Medical Center

Date created

• 2018-04-07

Resource type

• Major Qualifying Project

Major

• Biochemistry

Rights statement

• In Copyright