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Effect of Hydration on the Molecular Dynamics of Hydroxychloroquine Sulfate

Publication Type
Journal Name
ACS Omega
Publication Date
Page Numbers
21231 to 21240

Known primarily as antimalaria drugs, chloroquine and its derivative hydroxychloroquine have been also used as immunosuppressants, considered for antitumor therapy, and recently attracted attention and debate as potential antiviral agents for treatment of the coronavirus disease (COVID-19). Here, we investigate the influence of hydration water on the molecular dynamics in hydroxychloroquine sulfate, a commonly used solubilized drug form. When the hydration, even at a low level, results in a disordered structure, as opposed to the highly ordered structure of dry hydroxychloroquine sulfate, the activation barriers for the rotation of methyl groups in the drug molecules become randomized and, on average, greatly reduced. The facilitated stochastic motions of the methyl groups may benefit the biomolecular activity due to the more efficient sampling of the energy landscape in the disordered hydration environment experienced by the drug molecules in vivo.