Non-competitive interactions between hydroxychloroquine and azithromycin: Systematic density functional, molecular...

Area of Science:

• Computational Chemistry
• Drug Interactions
• Molecular Modeling

Background:

• Hydroxychloroquine (HCQ) and azithromycin (AZTH) are drugs with potential applications against SARS-CoV-2.
• Understanding drug interactions is crucial for optimizing therapeutic strategies.

Purpose of the Study:

• To investigate the non-competitive interaction between HCQ and AZTH using computational methods.
• To elucidate the binding mechanisms of HCQ and AZTH with SARS-CoV-2 targets.

Main Methods:

• Density Functional Theory (DFT) calculations were employed to study molecular interactions.
• Molecular docking simulations were performed to assess binding affinities and sites.
• Thermodynamic parameters like Gibbs free energy and enthalpy were calculated.

Main Results:

• Calculated Gibbs free energy and enthalpy changes were positive, indicating non-spontaneous HCQ-AZTH complex formation in water.
• Docking studies revealed distinct binding sites for HCQ and AZTH on SARS-CoV-2 main protease and ACE2 proteins.
• The combined HCQ-AZTH structure exhibited enhanced electrochemical properties.

Conclusions:

• HCQ and AZTH do not spontaneously form a complex in aqueous media.
• The drugs target different sites on viral and host proteins, suggesting a non-competitive interaction.
• Synergistic effects between HCQ and AZTH are possible, potentially enhancing therapeutic efficacy against SARS-CoV-2 without adverse interactions.