SARS-CoV-2 virion physicochemical characteristics pertinent to abiotic substrate attachment

Abstract

The structure, size, and main physicochemical characteristics of the SARS-CoV-2 virion with the spike transmembrane protein corona were discussed. Using these data, diffusion coefficients of the virion in aqueous media and in air were calculated. The structure and dimensions of the spike protein derived from molecular dynamic modeling and thorough cryo-electron microscopy measurements were also analyzed. The charge distribution over the molecule was calculated and shown to be largely heterogeneous. Although the stalk part is negatively charged, the top part of the spike molecule, especially the receptor binding domain, remains positively charged for a broad range of pH. It is underlined that such a charge distribution promotes the spike corona stability and enhances the virion attachment to receptors and surfaces, mostly negatively charged. The review is completed by the analysis of experimental data pertinent to the spike protein adsorption at abiotic surfaces comprising nanoparticle carrier particles. It is argued that these theoretical and experimental data can be used for developing quantitative models of virus attachment to surfaces, facilitating adequate analysis of future experimental results.

Keywords: Adsorption of spike protein; Charge distribution over spike protein; Receptor attachment of spike protein; SARS-CoV-2 virion; Spike protein; Structure of SARS-CoV-2 virion.

Figure 1

A schematic representation of a SARS-CoV-2 particle (a), obtained using CellPAINT software [14], slices through tomographic reconstructions of SARS-CoV-2 virions (b), reprinted with permission from Turoňová et al. [15], scale bar, 30 nm.

Figure 2

Cryo-EM subtomogram average of the ectodomain of S protein shown as slices through the reconstruction (a), reprinted with permission from Turoňová et al. [15], scale bars, 5 nm. The original visual representation of S glycoprotein derived based on molecular structure provided in the study by Casalino et al. [22] with marked dimensions (b). Atoms are presented as spheres of Van der Waals radius. Protein and N-glycans are highlighted in orange and blue, respectively.

Figure 3

Charge distribution of the SARS-CoV-2 S glycoprotein, (a) top view, (b) side view, and (c) the charge distribution in the direction z, perpendicular to the virus surface. The ΣQ denotes the total electrostatic (partial) charge in 1-nm thick slice. Red and blue colors denote negative and positive charges, respectively. Snapshots were made based on molecular coordinates provided in the study by Casalino et al. [22].

Figure 4

The nominal charge of the RBD of SARS-CoV-2 S protein [37] (highlighted red in the inset) versus pH, determined using the PROPKA algorithm. The black dashed line denotes data of nominal charge versus pH for the myoglobin molecule taken from the study by Batys et al. [38].