In this article, the Australian authors used surface spectroscopy, electrochemical and single-molecule scanning tunneling microscopy-break junction (STMBJ) technique to electrically detect the spike (S) protein, and to investigate the chemical reactivity of SARS-CoV-2 with different surfaces of electrodes. They also assessed the effect of electric field on the S protein at the single-molecule level. The results showed that S protein is electrically conductive, it reacts with gold, silicon, copper, and platinum electrodes and denatures. These findings open new possibilities for the development of coronavirus-capturing materials.
The structures of the S proteins of most of the coronaviruses, including SARS-CoV-2, have multiple disulfide (S–S) bonds. The S–S bonds are likely to be present in the future types of coronaviruses and variants. The S1 and S2 subunits of the S protein contain 14 S–S bonds in well-defined regions. The S1 subunit is composed of the receptor binding domain (RBD) that contains 4 S–S bridges, the N-terminal domain (NTD) that contains 3 S–S bridges and the S1/S2 cleavage site that contains 3 S–S bridges.
The abundance of S–S bridges indicate their important structural role in the formation and stabilization of the S protein architecture. These S–S bonds are essential to the ability of the SARSCoV-2 S protein to infect a host cell, by interacting with the angiotensin-converting enzyme 2 (ACE2) cell surface receptor.
About the study
The authors used surface spectroscopy, electrochemical and single-molecule scanning tunneling microscopy-break junction (STMBJ) technique to electrically detect the S protein, and to investigate the chemical reactivity of SARS-CoV-2 with different surfaces of electrodes. They also assessed the effect of electric field on the S protein at the single-molecule level.
The results demonstrated that S protein reacts and forms covalent bonds with specific metals and silicon (Si) electrodes. The disulfide (S–S) bonds of the S1 subunit reacted with gold (Au) and Si electrodes. Bonding to Si was induced by a spontaneous electrochemical reaction, which involved the oxidation of Si–H and the reduction of the S–S bonds. By contrast, there was no covalent bonding between the S1 protein and plastic or stainless steel. The S1 protein was only physically adsorbed on these surfaces.
The results also showed that the S1 subunit was highly conductive at the single molecule level. The conductance of a single S1 protein was surprisingly high and ranged between two states of 3 × 10−4G0 and 4 × 10−6G0 (1G0 = 77.5 µS). These two conductance states were governed by the reaction of the S–S bonds with Au, which controls the orientation of the protein in the circuit.
Clear conductance signals were observed only in electric fields equal to or lower than 7.5 × 107 V m−1. In an electric field of 1.5 × 108 V m−1, the original conductance magnitude decreased, which was accompanied by a lower junction yield.
Above an electric field of 3 × 108 V m−1, junctions with the S1 protein were not observed. The conducting channels were blocked, and the disappearance of the protein’s current signature at such field magnitudes was attributed to the denaturation of the protein. This leads to the blocking of the electron channels across the protein, and the unfavorable orientation of the S protein in the junction at high electric fields, which can also lead to the blocking of the electron channels.
These results showed that S protein is electrically conductive, it reacts with gold, silicon, copper, and platinum electrodes. These materials potentially may be used to develop anti-coronavirus surfaces, which are capable to irreversibly trap the virus via strong covalent bonds. This could explain why SARSCoV-2 survives only a limited time on copper, compared to its viability on stainless steel or plastics.
These findings open new venues for developing coronavirus-capturing materials and offer an electrical method for analyzing, detecting and potentially electrically deactivating persistent and future variants of SARS-CoV-2. Because all future coronaviruses will possess peripheral disulfide bonds in their S proteins, the reaction of SARS-CoV-2 disulfide (S–S) bonds with metals and Si is of great importance.
This article was published in the scientific journal Chemical Science.Â
Journal Reference
Dief EM and Darwish N. SARS-CoV-2 spike proteins react with Au and Si, are electrically conductive and denature at 3 × 108 V m−1: a surface bonding and a single-protein circuit study. Chem Sci, 2023, 14, 3428
https://doi.org/10.1039/d2sc06492h