Design of Angiotensin-converting Enzyme 2 (ACE2) Inhibitors by Virtual Lead Optimization and Screening

Area of Science:

• Medicinal Chemistry
• Computational Drug Design
• Pharmacology

Background:

• Angiotensin-converting enzyme 2 (ACE2) is a key target for cardiorenal diseases and viral infections.
• Developing novel therapeutics against ACE2 remains a critical area of research.

Purpose of the Study:

• To computationally design and screen drug-like molecules with high affinity for ACE2.
• To identify potential antiviral drug candidates with favorable pharmacokinetic and safety profiles.

Main Methods:

• Molecules were designed using SYBYL's LeapFrog module for ACE2 affinity.
• In silico screening using Molinspiration, Molsoft, and OSIRIS evaluated oral bioavailability and potential side effects.
• Quantitative Structure-Activity Relationship (QSAR) models were developed and validated.

Main Results:

• Seven drug candidates targeting ACE2 were identified after multi-stage screening.
• QSAR models demonstrated high predictive power with q² = 0.652 and r² = 0.962.
• The designed ligands are suitable for subsequent in vitro and in vivo investigations.

Conclusions:

• The study successfully designed novel ACE2-targeting molecules with potential therapeutic applications.
• These candidates represent promising leads for developing new treatments for viral infections and cardiorenal conditions.