Water-SARS-CoV-2 Interaction-Based Mechanism Inhibiting Virus Attachment to Host Cells

Many studies showed that the enveloped viruses, including coronaviruses, HIV-1, and influenza inactivate significantly faster in water than the non-enveloped viruses. It looks that there is a certain mechanism controlling this phenomenon. However, the epidemic spread of SARS-CoV-2 indicates that this virus – water interaction mechanism is not effective enough to fully inhibit coronavirus reproduction. We hypothesized that a spatially extended layer of the ordered water molecules, formed around CoV due to the spike’s glycans – surrounding water interaction acts as a buffer inhibiting CoV motion and its attachment to the host cell receptor. There is experimental evidence that water molecules while interacting with glucans experience the long-range ordering and repulsive forces. Our findings revealed new features that can promote its interaction. It was shown that the glycans and water molecules have the same far ultraviolet (UV) absorbance peak at ~185 nm. This peak is a manifestation of the still little-known physical properties possessed by hydroxyl (OH) groups, including those contained in glycans and water molecules. Many studies show that the carbohydrate hydroxyl groups are a key element in the long-range antifreeze glycoproteins activity which is closely correlated with our issue. To further increase ice inhibition, a sugar-based (usually trehalose) water solution, further slowing down the water dynamics is commonly used. Our experiments with sugar-based compounds dissolved in water showed that in such solutions the UV absorbance at ~185 nm (activity of the OH groups) can be essentially increased with respect to the bulk water. The spike’s glycans – water long-range interaction, activated due to the dissolved sugar-based compound, creates the glass-like stabilizing hydration layer (like in case of the trehalose) effectively inhibiting the virus – host cell binding. It was shown that the chemical structures of the known compounds with proven inhibition of SARS-CoV-2 entry into host cells agree with our findings. The described approach can be effective against human immunodeficiency viruses, influenza viruses, and possibly other enveloped viruses.