Repurposing Hydroxychloroquine as a Model Drug for the Prediction of Potential SARS-CoV-2 Inhibitor

Abstract

The use of hydroxychloroquine as SARS-CoV-2 inhibitor is currently being reviewed in various clinical trials. To exhaustively assess the benefit of hydroxychloroquine in the search for SARS-CoV-2 cure, this paper repositioned hydroxychloroquine as a model for virtual screening on the ZINC database. Molecular docking studies of 5r7y with the retrieved molecules were performed. The S-score of the predicted compounds were compared with the reference inhibitor (hydroxychloroquine). After evaluating their binding energy, five compounds (ZINC52939663, ZINC21291670, ZINC12714071, ZINC40089978 and ZINC15963294) were noticed have to highest binding energy with SARS-CoV-2. The binding scores of the top five ligands were higher than that of the reference molecule. The pharmacokinetics, toxicity prediction, drug-likeness and global reactivity assessment of ZINC52939663, present the lead compound as a drug candidate with the probable capacity to inhibit SARS-CoV-2.

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

“…Smaller E g means softer structures with smaller chemical hardness, η = – ( E HOMO – E LUMO )/2, as can be seen from table 1 . Drugs with smaller η are pharmaceutically favorable due to their ability to exchange charges with the target proteins [ 45 , 46 , 52 , 53 ]. We can involve η in some quantitative expressions related to the electrophilicity ω = μ 2 /2η, where the chemical potential μ = ( E HOMO + E LUMO )/2 from which the electronegativity is defined as χ = – μ.…”