Chloroquine and Hydroxychloroquine Inhibitors for COVID-19 Sialic Acid Cellular Receptor: Structure, Hirshfeld Atomic Charge Analysis and Solvent Effect
COVID-19, the pandemic disease recently discovered in Wuhan (China), has spread severely and has affected social and economic activity around the world. Attempts to find an effective vaccine are difficult, time consuming, but interminable. Therefore, the proposal of new effective drugs is a reliable and effective alternative. Given the similarity of the COVID-19 genome to SARS-CoV, drugs with safety profiles could be a quick fix. Clinical trials have encouraged the use of chloroquine and hydroxychloroquine for inhibition of COVID-19. One of the possible inhibitory pathways is competitive binding with angiotension converting enzyme-2 (ACE-2), in particular with cellular sialic acid (Neu5Ac). Here, we investigate the possible binding mechanism of ClQ and ClQOH with sialic acid both in gas phase and in water using density functional theory (DFT). We studied the binding of neutral, monoprotonated and diprotonated ClQ and ClQOH to sialic acid to simulate the effect of pH on cell receptor binding. The DFT results reveal that monoprotonated ClQ + and ClQOH +, which make up more than 66% of the solution, have high reactivity and binding to sialic acid. The Neu5Ac-ClQ adducts and the Neu5Ac-ClQOH analogs were stabilized in water than in the gas phase. Molecular complexes stabilize by strong hydrogen bonding and π - π stacking forces. In addition, the transfer of protons into Neu5Ac-ClQOH + provides more stabilizing power and binding forces to cell recognition. These findings highlight a possible recognition mechanism and help future breakthroughs for COVID-19 inhibitors.
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