Domingo and Faraudo performed all atomic simulations between the SARS-CoV-2 spike glycoprotein and human skin models. They considered an “oily” skin covered by sebum and a “clean” skin exposing the stratum corneum. The simulations showed that the spike tries to maximize the contacts with stratum corneum (SC) lipids, particularly ceramides, with substantial hydrogen bonding. While, in the case of “oily” skin, the spike is able to retain its structure, orientation and hydration over sebum with little interaction with sebum components. Their study recently appeared in BioRxiv.
Several experimental studies showed that the SARS-CoV-2 virus is able to survive infectious adsorbed over human skin for about 10 hours, much longer than typical survival time for influenza virus (∼ 1 − 2 hours). These studies also showed that SARS-CoV-2 virus adsorbed onto skin are inactivated within 15 seconds upon treatment with ethanol based disinfectants, emphasizing the importance of correct hand hygiene protocols. The reason for this long stability of the SARS-CoV-2 virus over human skin is still unknown. In fact, at the present time, there is a lack of fundamental understanding of fundamental aspects of the interactions between coronaviruses and surfaces at the physicochemical level. This is in fact motivated Domingo and Faraudo to elucidate the molecular details of the interaction between SARS-CoV-2 virus and human skin.
They have performed a total of four different simulations (i.e. two models, one for stratum corneum (SC) and another for sebum): SC and water droplet, SC and hydrated spike, Sebum and water droplet and Sebum and hydrated spike, which correspond to wetting simulations of the two skin models (placement of a water droplet on top of each skin model) and their interaction with the S protein. In addition to these simulations, they have performed an additional simulation of the interaction of the spike protein with a POPC layer (a common phospholipid present in animal cell membrane) as a reference for the interaction between the protein and a lipid bilayer.
“We will distinguish between two different situations. One case corresponds to clean skin in body regions without hair and without sebaceous glands, such as the palms of the hands. In this case, the exposed surface of the skin corresponds to the outermost layer of the epidermis, the so called stratum corneum (SC). The opposite case corresponds to skin covered by a protective oily or waxy layer known as sebum, which is segregated by the sebaceous glands, which are present in large numbers in our face, for example. Sebum can be present not only in regions of the skin with sebaceous glands but also in other body parts (for example fingers) in which sebum has been transferred by touching other skin regions covered by sebum.”
Their simulation results showed striking differences between the two cases. In the case of stratum corneum lipids, the spike protein adsorbs with its long axis almost parallel to the lipid surface, maximizing the contact between the spike and the stratum corneum surface.
While, in the case of sebum, the spike protein adsorbs retaining its original perpendicular orientation, with the Receptor Binding Domain (RBD) of the three monomers of the spike oriented towards the sebum surface.
Interestingly, the behaviour of the hydration of the spike protein also differs in both cases. In the case of stratum corneum, they observed a full wetting of the SC bilayer which may compite with the tendency of spike to remain hydrated, thus producing a tension that may affect the orientation of spike over SC. While, in the case of the spike protein adsorbed onto sebum, spike is maintained inside a well-defined hydration droplet formed on top of the sebum layer.
“These results are consistent with our simulation results for the wetting behaviour of both surfaces, in which we obtain a much smaller contact angle for a water droplet on top of stratum corneum as compared with sebum.”
They also found that the spike protein has also a tendency to interact differently with the different molecules present in their stratum corneum and sebum models. They observed a stronger interaction of the spike(higher number of protein-molecule contacts) with those skin molecules with higher hydrogen bonding ability: ceramides in the case of stratum corneum and triglyrecides in the case of sebum.
The number of hydrogen bonds between the spike protein and skin molecules is much larger in the case of stratum corneum as compared with sebum. Also, it has been noted that in the case of sebum, the number of hydrogen bonds with the spike protein is comparable with that obtained in previous simulations of the interaction between the spike and cellulose, which is a remarkable result given the high tendency of cellulose to form hydrogen bonds. They do not observe a significant deformation or structural change of the spike protein after interaction with both skin models. This is in sharp contrast with their previous results obtained for the interaction between the spike protein and solid surfaces (cellulose and graphite).
Finally, they compared the results obtained for the different surfaces with their previous simulations of the interaction of SARS-CoV-2 spike with hydrophilic and hydrophobic surfaces. Their results indicated that in the case of solid surfaces the protein tends to change in order to increase the interaction with the surface, whereas in the case of soft surfaces the optimization of the protein-surface interaction can be achieved by a small deformation of the surface. This suggested that the “soft” or “hard” nature of surface plays an important role alongwith, wetting and hydrogen bonding properties.
Featured image: Scheme of the role of skin in the indirect transmission of a virus particle via contaminated surfaces. The sneezing or coughing of an infected individual can contaminate a surface or directly the skin of another individual. The virion may remain intact and infectious over the skin (either a sebaceous, oily skin or a clean skin with the stratum corneum exposed) so the individual can be then infected by touching their eyes mouth or nose. Scheme created with BioRender.com © Domingo and Faraudo
Reference: Marc Domingo, Jordi Faraudo, “Interaction between SARS-CoV-2 spike glycoprotein and human skin models: a molecular dynamics study”, bioRxiv 2021.07.13.452154; doi: https://doi.org/10.1101/2021.07.13.452154
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