Search

• Molecular interactions between sialic acid (Neu5Ac) with Chloroquine (ClQ) and hydroxychloroquine (ClQOH) in the gas phase and water. • Water facilitates the charge transfer from Neu5Ac to ClQ and ClQOH that enhanced molecular recognition. • The monoprotonated forms Neu5Ac-ClQ+ and Neu5Ac-ClQOH+ were the most stable adducts. • Hydrogen bonding dominated the molecular recognition forces for the molecule adducts, except Neu5Ac-ClQOH+ that stabilized by the proton transfer process. COVID-19, the pandemic disease recently discovered in Wuhan (China), severely spread and affected both social and economic activity all over the world. Attempts to find an effective vaccine are challenging, time-consuming though interminable. Hence, re-proposing effective drugs is reliable and effective alternative. Taking into account the genome similarity of COVID-19 with SARS-CoV, drugs with safety profiles could be fast solution. Clinical trials encouraged the use of Chloroquine and Hydroxychloroquine for COVID-19 inhibition. One of the possible inhibition pathways is the competitive binding with the angiotension-converting enzyme-2 (ACE-2), in particular with the cellular Sialic acid (Neu5Ac). Here, we investigate the possible binding mechanism of ClQ and ClQOH with sialic acid both in the gas phase and in water using density functional theory (DFT). We investigated the binding of the neutral, monoprotonated and diprotonated ClQs and ClQOHs to sialic acid to simulate the pH effect on the cellular receptor binding. DFT results reveals that monoprotonated ClQ+ and ClQOH+, which account for more than 66% in the solution, possess high reactivity and binding towards sialic acid. The Neu5Ac-ClQ and the analogues Neu5Ac-ClQOH adducts were stabilized in water than in the gas phase. The molecular complexes stabilize by strong hydrogen bonding and π - π stacking forces. In addition, proton-transfer in Neu5Ac-ClQOH+ provides more stabilizing power and cellular recognition binding forces. These results shed light on possible recognition mechanism and help future breakthroughs for COVID-19 inhibitors. Image, graphical abstract [ABSTRACT FROM AUTHOR]