Unraveling the impact of binary vs. ternary alcohol solutions on the conformation and solvation of the SARS-CoV-2 receptor-binding domain†

Abstract

The use of alcohol as hand sanitizer to prevent the spread of contamination of SARS-CoV-2 is known. In this work, a series of atomistic molecular dynamics (MD) simulations were carried out with the receptor-binding-domain (RBD) of SARS-CoV-2 in different aqueous binary and ternary mixtures of concentrated ethanol, n-propanol (n-pr), and iso-propanol (iso-pr) solutions to elucidate the structural alteration of RBD at ambient and elevated temperature and to understand RBD's interactions with the host cellular receptor ACE2. Computation of several structural metrics like RMSD, R_g, and fraction of native contacts along with the construction of a 2D-free energy landscape suggests that among all the water–alcohol(s) solutions, the structural transition of RBD conformation was more pronounced in the water–etoh–iso-pr mixture under ambient conditions which further altered significantly and RBD adopted partially unfolded states at 350 K, as compared to the native form. We observed that the preferential exclusion of different alcohols from the RBD surface regulates the solvation features of RBD and hence the RBD–alcohol hydrogen bonds, which is one of the crucial factors that rupture RBD's structure heterogeneously. From the comparative study, it was inferred that relative to binary mixtures, the ternary solutions rupture the native RBD structure more effectively which was caused by the relative reduction in dynamics in the ternary mixture for the particular pair of hydrogen bonds arising from the hindered rotation of certain alcohol molecules. Our microscopic investigation identified that the specific binding zone was disrupted remarkably, and as a result, the contact distances between the deformed binding zone of RBD and ACE2 were found to increase from the molecular docking study; this could prevent further transmission.