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

Abstract

Developing means to characterise SARS-CoV-2 and its new variants is critical for future outbreaks. SARS-CoV-2 spike proteins have peripheral disulfide bonds (S–S), which are common in all spike proteins of SARS-CoV-2 variants, in other types of coronaviruses (e.g., SARS-CoV and MERS-CoV) and are likely to be present in future coronaviruses. Here, we demonstrate that S–S bonds in the spike S1 protein of SARS-CoV-2 react with gold (Au) and silicon (Si) electrodes. Bonding to Si is induced by a spontaneous electrochemical reaction that involves oxidation of Si–H and the reduction of the S–S bonds. The reaction of the spike protein with Au enabled single-molecule protein circuits, by connecting the spike S1 protein between two Au nano-electrodes using the scanning tunnelling microscopy-break junction (STM-BJ) technique. The conductance of a single spike S1 protein was surprisingly high and ranged between two states of 3 × 10⁻⁴G₀ and 4 × 10⁻⁶G₀ (1G₀ = 77.5 μS). The two conductance states are governed by the S–S bonds reaction with Au which controls the orientation of the protein in the circuit, and via which different electron pathways are created. The 3 × 10⁻⁴G₀ level is attributed to a single SARS-CoV-2 protein connecting to the two STM Au nano-electrodes from the receptor binding domain (RBD) subunit and the S1/S2 cleavage site. A lower 4 × 10⁻⁶G₀ conductance is attributed to the spike protein connecting to the STM electrodes from the RBD subunit and the N-terminal domain (NTD). These conductance signals are only observed at electric fields equal to or lower than 7.5 × 10⁷ V m⁻¹. At an electric field of 1.5 × 10⁸ V m⁻¹, the original conductance magnitude decreases accompanied by a lower junction yield, suggesting a change in the structure of the spike protein in the electrified junction. Above an electric field of 3 × 10⁸ V m⁻¹, the conducting channels are blocked and this is attributed to the spike protein denaturing in the nano-gap. These findings open new venues for developing coronavirus-capturing materials and offer an electrical method for analysing, detecting and potentially electrically deactivating coronaviruses and their future variants.