Molecular Docking Study of the Binding Interaction of Hydroxychloroquine, Dexamethasone and Other Anti-Inflammatory Drugs with SARS-CoV-2 Protease and SARS-CoV-2 Spikes Glycoprotein

Abstract

Aims: The outbreak of the novel coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking; 2) assessing drug toxicity profiles using biological data; 3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. Methods: 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug's canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety; steric clashes and voids in the binding site were also analysed. Results and discussion: Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen.

Biological efficacy of novel metal complexes of Nitazoxanide: Synthesis, characterization, anti-COVID-19, antioxidant, antibacterial and anticancer activity studies

“…Currently, a molecular docking procedure is used to predict the biological efficiency of the molecules and estimate the preferred ligand orientation when it binds to the site pocket on the targeted protein [22] . Initially, all metal complexes exhibited better binding affinities to both proteinases than the free NTZ.…”

“…Among the three interaction types, the ionic interaction of NH in the Au(III) molecule with the ASP287 amino acid had a bond strength of -4.4 kcal/mol. Interestingly, we also docked the investigated compounds against 6VXX on the S2 subunit pocket (686–1273), which is responsible for cell membrane fusion [22] and the results showed that NTZ-Ag(I) is more effective among the tested complexes. In this practical interaction, shown in Table 3 , Ag(I) metal binding to the ASP 867 amino residue was observed, along with hydrophobic pi-H binding between NH in the ligand moiety and HIS 1058.…”

“…The active sites were located with the MOE-Site finder tool and expressed as dummy atoms by the application. The protein SARS-CoV-2 spike glycoprotein (PDB ID: 6VXX) has 1273 amino acids, and we chose the S1 subunit (14–685) as a binding pocket in charge of receptor binding during viral infection [22] . The optimized geometries for the metal complex files were converted to MDB files and saved as a database.…”