In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House,...

Area of Science:

• Computational chemistry and drug discovery
• Virology and molecular biology
• Pharmacology

Background:

• The SARS-CoV-2 pandemic highlighted the need for effective antiviral strategies.
• The main protease (Mpro, also known as 3CLpro) is essential for SARS-CoV-2 replication and a primary therapeutic target.
• Developing novel Mpro inhibitors is crucial for pandemic control.

Purpose of the Study:

• To identify potent drug-like compounds targeting the SARS-CoV-2 Mpro protease using computer-aided drug design (CADD).
• To screen in-house and commercial compound databases for potential Mpro inhibitors.
• To validate the efficacy and stability of identified lead compounds.

Main Methods:

• Structure-based virtual screening (SBVS) using MOE software against SARS-CoV-2 Mpro.
• Molecular docking of promising virtual screening hits to assess binding affinity.
• Molecular dynamics simulations (MDS) to evaluate the stability of protein-ligand complexes.

Main Results:

• Virtual screening identified multiple hits from in-house and commercial databases.
• Several potent lead compounds with significant binding affinity to Mpro were selected.
• Molecular dynamics simulations confirmed the stability of the identified complexes and their interaction with the catalytic dyad.

Conclusions:

• The study successfully identified potential lead compounds for SARS-CoV-2 Mpro inhibition using CADD.
• The selected scaffolds show promise for future antiviral drug development against coronaviruses.
• Further preclinical and clinical research is necessary to confirm the therapeutic potential of these compounds.