Abstract: Journal of King Saud University – Science 33 (2021) 101334 Contents lists available at ScienceDirect Journal of King Saud University – Science journal homepage: www.sciencedirect.com Original article Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations Olfa Noureddine a, Noureddine Issaoui a,⇑, Mouna Medimagh a, Omar Al-Dossary b,⇑, Houda Marouani c a b c University of Monastir, Laboratory of Quantum and Statistical Physics (LR18ES18), Faculty of Sciences, Monastir 5079, Tunisia Department of Physics and Astronomy, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia University of Carthage, Laboratory of Chemistry of Materials (LR13ES08), Faculty of Sciences of Bizerte, 7021, Tunisia a r t i c l e i n f o Article history: Received 5 December 2020 Revised 21 December 2020 Accepted 25 December 2020 Available online 6 January 2021 Keywords: DFT method Structural analysis HOMO-LUMO MEP Molecular docking calculations a b s t r a c t Structure
activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. The geometric were determined and compared with the experimental crystal structure. The intra and intermolecular interactions which exist within these compounds are analyzed by different methods namely the topological analysis AIM, ELF and the reduced gradient of the density. These approaches make it possible in particular to study the properties of hydrogen bonds. The highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The densities of state diagrams were determined to calculate contributions to the molecular orbitals. The molecular electrostatic potential surfaces are determined to give a visual representation of charge distribution of these ligands and to provide information linked to electrophilic and nucleophilic sites localization. Finally, these derivatives were evaluated for the inhibition of COVID-19 activity by using the molecular docking method. Ó 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Rationale Over the past two decades, several infectious diseases caused by various viruses have occurred frequently, what affecting not only the life of human beings, but also affecting national security and stability. At the beginning of the year, Coronavirus disease 2019 namely COVID-19 is a contagious disease caused by a novel strain of beta-coronavirus called SARS-CoV-2 or 2019-nCoV (Huang et al., 2019) that had never been known in humans before. This new ⇑ Corresponding authors. E-mail addresses: issaoui_noureddine@yahoo.fr (N. Issaoui), omar@ksu.edu.sa (O. Al-Dossary). Peer review under responsibility of King Saud University. Production and hosting by..