Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease

Area of Science:

• Drug Discovery and Development
• Computational Chemistry
• Virology

Background:

• No unique, highly effective, and safe drug candidates specifically targeting SARS-CoV-2 are currently available.
• Existing treatments often involve repurposed drugs or compounds with limitations in efficacy or safety.

Purpose of the Study:

• To identify novel, commercially available compounds with high efficacy and safety profiles against SARS-CoV-2.
• To evaluate the potential of ZINC07333416 as an anti-COVID-19 therapeutic agent.

Main Methods:

• Molecular docking studies were performed to assess the binding affinity of ZINC07333416 to the SARS-CoV-2 main protease (Mpro).
• Molecular dynamics simulations (MDS) were utilized to confirm the stability of the protein-ligand interaction.
• Virtual assessment of medicinal chemistry, pharmacokinetics, and synthetic accessibility was conducted.

Main Results:

• ZINC07333416 demonstrated a superior binding energy (-8.72 kcal/mol) to SARS-CoV-2 Mpro compared to Lopinavir, Remdesivir, and hydroxychloroquine.
• The compound formed crucial interactions with key active site residues (Cys145, His41) and dimerization residues (Glu-166, Asn-142) of Mpro.
• MDS confirmed the stable interaction between ZINC07333416 and SARS-CoV-2 Mpro.

Conclusions:

• ZINC07333416 is a promising, commercially available compound with significant potential as an antiviral agent against COVID-19.
• Its favorable virtual assessment in medicinal chemistry, pharmacokinetics, and synthetic accessibility supports further experimental validation.