COVID-19 is transmitted by inhaling airborne droplets containing coronavirus SARS-CoV-2 virions, which represent spheroidal nanoparticles, with a lipid bilayer envelope of about 85 nanometer diameter decorated by a “crown” of 20 nanometer long Spike protein protrusions. In the respiratory tract, the virions interact with surfactant films composed of lipids and cholesterol that coat lung airways. Here, we explore by using coarse-grained molecular dynamics simulations the physico-chemical mechanisms of adsorption of lung and exogenous surfactants on S1 domain of the Spike protein that is responsible for binding with ACE2 receptors and virus transmission into the cells. Simulations are performed with three typical surfactants and their mixtures, zwitterionic dipalmitoyl phosphatidyl choline (DPPC) lipid and amphipathic cholesterol (CHOL) that are main components of lung surfactant films and exogenous anionic surfactant sodium dodecyl sulphate (SDS). It is found that surfactant adsorption is associated with the formation of surfactant aggregates that adhere to specific regions of S1 domain, which have preferential affinity to surfactant adsorption. The distribution of adsorbed surfactants along the S1 residue sequence is characterized by the probabilities of adsorption on individual residues. Cholesterol exhibits distinctively higher adsorption that is consistent with recent experimental observations. Anionic surfactants have a higher affinity to S1 receptor binding domain, tending to be adsorbed on cationic Arginine and Lysine residues, which are present in higher quantities in CoV-2 Delta and Omicron variants. The latter effect may have important implications for the search of extraneous therapeutic surfactants that can potentially inhibit binding of SARS-CoV-2 virions with ACE2 receptors and virus intracell transmission.

Exploring surfactant adsorption on SARS-CoV-2 Spike protein by coarse-grained molecular dynamics simulations

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