The transmission of SARS-CoV-2 coronavirus has led to the COVID-19 pandemic. Nucleic acid testing while specific has limitations for mass surveillance. One alternative is the main protease (M pro ) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect M pro via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C-/N-terminus to exploit the specific recognition by M pro . Autolytic cleavage releases a positively charged moiety that assembles the nanoparticles with rapid color changes (t < 10 min). We determine a limit of detection for M pro in breath condensate matrices < 10 nM. We further assayed ten COVID-negative subjects and found no false-positive result. In the light of simplicity, our test for viral protease is not limited to an equipped laboratory, but also is amenable to integrating as portable point-of-care devices including those on face-coverings.

As an important subfield of flexible electronics, conductive fibers have been an active area of research. The interfacial interaction between nanostructured conductive materials with elastic substrates plays a vital role in the electromechanical performance of conductive fibers. However, the underlying mechanism has seldom been investigated. Here, we propose a fabricating strategy for a silver nanowire (Ag NW)/polyurethane composite fiber with a sheath-core architecture. The interfacial bonding layer is regulated, and its influence on the performance of conductive fibers is investigated, based on which an interfacial interaction model is proposed. The model underlines the significance of the embedding depth of the Ag NW network. Both supersensitive (gauge factor up to 9557) and ultrastable (negligible conductance degradation below the strain of 150%) conductive fibers are obtained via interface regulating, exhibiting great potential in the applications of wearable sensors and stretchable conducting connections.

There is a need for surveillance of COVID-19 to identify individuals infected with SARS-CoV-2 coronavirus. Although specific, nucleic acid testing has limitations in terms of point-of-care testing. One potential alternative is the nonstructural protease (nsp5, also known as M pro /3CL pro ) implicated in SARS-CoV-2 viral replication but not incorporated into virions. Here, we report a divalent substrate with a novel design, (Cys) 2 –(AA) x –(Asp) 3 , to interface gold colloids in the specific presence of M pro leading to a rapid and colorimetric readout. Citrate- and tris(2-carboxyethyl)phosphine (TCEP)-AuNPs were identified as the best reporter out of the 17 ligated nanoparticles. Furthermore, we empirically determined the effects of varying cysteine valence and biological media on the sensor specificity and sensitivity. The divalent peptide was specific to M pro , that is, there was no response when tested with other proteins or enzymes. Furthermore, the M pro detection limits in Tris buffer and exhaled breath matrices are 12.2 and 18.9 nM, respectively, which are comparable to other reported methods (i.e., at low nanomolar concentrations) yet with a rapid and visual readout. These results from our work would provide informative rationales to design a practical and noninvasive alternative for COVID-19 diagnostic testing—the presence of viral proteases in biofluids is validated.