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

Mohammed A H Khalafalla; Chokri Hadj Belgacem; Ismail Abdelrehim; Kamel Chaieb

doi:10.1016/j.cplett.2021.138745

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

Chem Phys Lett. 2021 Aug 16:777:138745. doi: 10.1016/j.cplett.2021.138745. Epub 2021 May 18.

Authors

Mohammed A H Khalafalla¹, Chokri Hadj Belgacem¹, Ismail Abdelrehim², Kamel Chaieb³

Affiliations

¹ Department of Physics, Faculty of Science, Yanbu, Taibah University, Yanbu, Saudi Arabia.
² Department of Biology, Faculty of Science, Yanbu, Taibah University, Yanbu, Saudi Arabia.
³ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

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.

Keywords: Azithromycin; Density functional theory; Hydroxychloroquine; Molecular docking; SARS-CoV-2.