First COVID-19 molecular docking with a chalcone-based compound: synthesis, single-crystal structure and Hirshfeld...

Area of Science:

• Medicinal Chemistry
• Structural Biology
• Computational Chemistry

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) main protease (Mpro) is a critical target for COVID-19 drug development.
• Chalcone derivatives are known for their diverse biological activities, including antiviral properties.

Purpose of the Study:

• To report the first molecular docking study of a novel chalcone-based ligand with SARS-CoV-2 Mpro (PDB ID: 7BQY).
• To characterize the binding interactions and affinity of the chalcone ligand with the Mpro active site.
• To present the synthesis, crystal structure, and spectral analysis of the chalcone compound.

Main Methods:

• Molecular docking simulations using rigid and flexible ligand binding modes.
• Analysis of binding interactions using LIGPLOT and visualization of ligand-receptor complexes.
• Synthesis and characterization of the chalcone compound, including single-crystal X-ray diffraction and Hirshfeld surface analysis.

Main Results:

• The chalcone ligand exhibited a high binding affinity of -7.0 kcal/mol with SARS-CoV-2 Mpro (7BQY).
• Key interactions included a significant hydrogen bond and multiple hydrophobic interactions within the Mpro active site.
• The crystal structure revealed stacked molecules with π-π interactions.

Conclusions:

• The chalcone-based compound shows potential as an inhibitor of SARS-CoV-2 Mpro.
• The study provides insights into the structure-activity relationship of chalcone ligands for Mpro inhibition.
• Further investigation is warranted to explore the therapeutic efficacy of this chalcone derivative.