TYC Seminar: Interactions of Coronavirus Virions as Biological Nanoparticles with Respiratory Environment: Insight from Multiscale Molecular Simulations – Alex Neimark, Rutgers University

Room RODH 617 – Sargent Center Seminar room, Imperial 

TYC Seminar: Interactions of Coronavirus Virions as Biological Nanoparticles with Respiratory Environment: Insight from Multiscale Molecular Simulations – Alex Neimark – Rutgers University Share on X

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.

We explore by using coarse-grained molecular dynamics simulations the physico-chemical mechanisms of adsorption of selected pulmonary surfactants, zwitterionic dipalmitoyl phosphatidyl choline and cholesterol, and exogeneous anionic surfactant, sodium dodecyl sulfate, on the S1-domain of the Spike protein.  We show that surfactants form micellar aggregates that selectively adhere to the specific regions of the S1-domain that are responsible for binding with ACE2 receptors. We find distinctly higher cholesterol adsorption and stronger cholesterol-S1 interactions in comparison with other surfactants, that is consistent with the experimental observations of the effects of cholesterol on COVID-19 infection.  Distribution of adsorbed surfactant along the protein residue chain is highly specific and inhomogeneous with preferential adsorption around specific amino acid sequences.  We observe preferential adsorption of surfactants on cationic arginine and lysine residues in the receptor-binding domain (RBD) that play an important role in ACE2 binding and are present in higher amounts in Delta and Omicron variants, which may lead to blocking direct Spike-ACE2 interactions. Our findings of strong selective adhesion of surfactant aggregates to of Spike proteins have important implications for informing clinical search for therapeutic surfactants for curing and preventing COVID-19 caused by SARS-CoV-2 and its variants.

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