(211g) Selective Adsorption of Surfactants on Coronavirus Virions

COVID-19 pandemic has triggered broad research activities aiming at preventing and curing coronavirus disease. COVID-19 is transmitted by inhaling airborne SARS-CoV-2 virions, which represent biologically active nanoparticles of ~ 120 nm enveloped by a lipid bilayer decorated by a “crown” of Spike protein protrusions. In the respiratory tract, coronavirus virions interact with surfactant films composed of phospholipids and cholesterol that coat lung airways. Active clinical search is underway for physiological and exogenous surfactants that may adsorb on Spike proteins or dilute the lipid envelope affecting the virion ability to bind and penetrate the cells. While the knowledge on the biochemical structure, pathology, and antibody/drug interactions of SARS-CoV2 and its variants is quickly growing, the physico-chemical aspects of the virion interactions with the respiratory system environment and specifically with adsorbing surfactants have been sparsely addressed and are poorly understood. Here, we explore by using coarse-grained molecular dynamics simulations the mechanisms of surfactant adsorption on Spike proteins. With examples of zwitterionic dipalmitoyl phosphatidyl choline, cholesterol, and anionic sodium dodecyl sulfate, we show that surfactants form micellar aggregates that selectively adhere to the specific regions of S1 domain of the Spike protein that are responsible for binding with ACE2 receptors and virus transmission into the cells. We find distinctively higher cholesterol adsorption in comparison with other surfactants, which is consistent with recent experimental studies. Cationic residues, arginine and lysine, which are present in higher quantities in mutated Delta and Omicron variants, preferentially adsorb anionic surfactants that may block direct S1-ACE 2 interactions and hinder binding. Our findings of strong selective adhesion of surfactant aggregates to receptor-binding fragments of Spike proteins may have important implications for informing the clinical search for exogenous therapeutic surfactants for curing and preventing COVID-19 caused by SARS-CoV-2 and its variants.