Electrochemical Resonance of Molecular Motion Enabling Label-, Antibody-, and Enzyme-Free Detection of SARS-CoV-2.

In this work, we developed a method to detect two viral marker proteins, the main protease and the spike protein (S protein), of SARS-CoV-2, as well as a host marker, chemokine receptor 5 (CCR5), which is associated with the risk of developing the severe acute respiratory syndrome. This assay can be completed in two steps in a label-free fashion, yielding a "signal-on" signal readout, which usually cannot be attained by electrochemical label-free detection using no labels or markers to tag the target protein. The proposed assay also utilizes no antibodies or enzyme-based reagents. The method achieves this performance by moderating the frequency of electrochemical potential scanning such that the scanning rate keeps pace with, or "resonances" with, the molecular motion of the probe molecule. This method has been successfully applied to detect the three target proteins in serum samples collected from patients infected with SARS-CoV-2, and the results indicate a strong correlation with the risk of deteriorating into severe acute conditions after virus infection. Soon, the clinical application of this method may provide a low-cost but effective method for virus surveillance in the general public.