Non-competitive interactions between hydroxychloroquine and azithromycin: systematic density functional, molecular dynamics, and docking calculations

Khalafalla, Mohammed; Hadj Belgacem, Chokri; Abdelrehim, Ismail; Chaieb, Kamel

In this study, density functional theory (DFT) and docking calculations were systematically performed to study the non-competitive interaction between Hydroxychloroquine (HCQ) and azithromycin (AZTH). The calculated changes in Gibbs free energy and enthalpy (at 310 K) were positive, indicating the non-spontaneous formation of HCQ-AZTH specifically in water media. Docking calculation confirmed the obtained DFT result as evident from the different binding sites of both drugs to the SARS-CoV-2 main protease and human angiotensin-converting enzyme 2 (ACE2) proteins. The HCQ-AZTH structure revealed enhanced electrochemical properties, suggesting the synergy between HCQ and AZTH without affecting their therapeutic efficacy against SARS-CoV-2.