Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors

Area of Science:

• Virology
• Drug Discovery
• Medicinal Chemistry

Background:

• Current human immunodeficiency virus type 1 (HIV-1) protease inhibitors have limitations due to adverse effects like metabolic complications.
• Developing novel, potent, and safer HIV-1 protease inhibitors is crucial for effective treatment.
• Drug repurposing offers an efficient strategy to accelerate the discovery of new therapeutic agents.

Purpose of the Study:

• To screen existing drugs for potential human immunodeficiency virus type 1 (HIV-1) protease inhibitory activity.
• To identify novel drug candidates with improved safety and efficacy profiles for HIV-1 treatment.
• To evaluate the binding affinity, stability, and therapeutic potential of repurposed drugs.

Main Methods:

• Screening of FDA-approved and investigational drugs from the DrugBank database.
• Utilizing molecular docking simulations to predict binding interactions with HIV-1 protease.
• Conducting in vitro anti-HIV-1 assays and XTT cell viability tests to assess efficacy and toxicity.

Main Results:

• CBR003PS and CBR013PS demonstrated significant binding affinity and stability with HIV-1 protease.
• Effective concentration (EC50) values were determined as 9.4 nM for CBR003PS and 36.6 nM for CBR013PS at 100% cell viability.
• Both compounds exhibited therapeutic indexes greater than 32, indicating a favorable safety profile.

Conclusions:

• CBR003PS and CBR013PS show significant potential for repurposing as novel HIV-1 protease inhibitors.
• These candidates offer a promising alternative to existing treatments due to their favorable therapeutic indexes.
• Further investigation into CBR003PS and CBR013PS could lead to the development of safer and more effective HIV-1 therapies.