Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus. Its genome encodes four structural proteins, namely the spike (S), envelope (E), nucleocapsid (N), and membrane (M) protein. In this article, the authors from Australia used several techniques to investigate the chemical reactivity of SARS-CoV-2 with diverse surfaces of electrodes. They also examined the impact of the electric field on the SARS-CoV-2 S protein at the single-molecule level. The results revealed that SARS-CoV-2 spike protein is electrically conductive, and reacts with gold, silicon, copper, and platinum electrodes and denatures.
The S protein plays three critical roles in facilitating host cell entry: it must bind the angiotensin-converting enzyme-2 (ACE2) receptor, be proteolytically processed, and promote membrane fusion. The S protein is a glycosylated homotrimer with each monomer composed of subunits S1 and S2. The S1 domain comprises an N-terminal domain (NTD), a receptor-binding domain (RBD) with a receptor binding motif (RBM), and two C-terminal domains. The RBD in the S1 subunit is a short immunogenic fragment responsible for attachment to host cells, mediating the interaction with the human ACE2 receptor. The S2 subunit contains the fusion machinery required for viral-cell membrane fusion.
The structures of the S proteins of most coronaviruses, including SARS-CoV-2, have multiple disulfide (S–S) bonds. The S1 and S2 subunits contain 14 S–S bonds in well-defined regions. The RBD in the S1 subunit contains four S–S bridges, the NTD contains three S–S bridges and the S1/S2 cleavage site contains three S–S bridges. The abundance of S–S bridges suggests that they play an important structural role in the S protein architecture formation and stabilization. It is believed that these S–S bonds are essential for the ability of the S protein to infect a host cell through its interaction with the ACE2 receptor.
About the study
The authors employed several techniques, including surface spectroscopy, electrochemical analysis, and scanning tunneling microscopy to investigate the chemical reactivity of SARS-CoV-2 with diverse surfaces of electrodes, and to detect the S protein electrically. They also assessed the impact of the electric field on the S protein at the single-molecule level.
The results showed that the S protein reacts and forms covalent bonds with specific metals and silicon (Si) electrodes. The disulfide bonds in the S1 subunit reacted with gold (Au) and Si electrodes. The bonding to Si was induced by a spontaneous electrochemical reaction that involved the oxidation of Si–H and the reduction of the disulfide bonds.
In contrast, there was no covalent bonding between the S1 subunit and plastic or stainless steel, and S1 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 disulfide bonds with Au, which controlled the orientation of the protein in the circuit.
Figure from the original article of Dief EM and Darwish N, 2023.
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. The authors attributed this disappearance of the protein’s current signature at these field magnitudes to the denaturation of the protein, leading to the electron channels blocking across the protein, and an unfavorable orientation of the S protein at high electric fields.
Conclusion
These findings revealed that the SARS-CoV-2 S protein is electrically conductive, and reacts with gold, silicon, copper, and platinum electrodes. In contrast, there was no covalent bonding between the S1 subunit and plastic or stainless steel, and S1 was only physically adsorbed on these surfaces. These findings may explain why SARSCoV-2 survives only a limited time on copper, in contrast to its viability on stainless steel or plastics.
Since all future coronaviruses will possess peripheral disulfide bonds in their S proteins, the reaction of SARS-CoV-2 disulfide bonds with metals and silicon is of great importance. These findings provide new opportunities for developing coronavirus-capturing materials capable of irreversibly trapping the virus via strong covalent bonds, and potentially electrically deactivating persistent and future variants of SARS-CoV-2.
This article was published in Chemical Science.
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
