A Charge-Switchable Zwitterionic Peptide for Rapid Detection of SARS-CoV-2 Main Protease

Angew Chem Int Ed Engl. 2022 Feb 21;61(9):e202112995. doi: 10.1002/anie.202112995. Epub 2022 Jan 14.

Abstract

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 (Mpro ) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect Mpro via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C-/N-terminus to exploit the specific recognition by Mpro . 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 Mpro 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.

Keywords: Colorimetric analysis; Covid-19; Smart mask; Zwitterionic peptide; mpro/3clpro/nsp5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Breath Tests
  • COVID-19 / diagnosis*
  • COVID-19 / virology
  • Colorimetry / methods
  • Coronavirus 3C Proteases / metabolism*
  • Humans
  • Limit of Detection
  • Peptides / metabolism*
  • Proteolysis
  • SARS-CoV-2 / metabolism*

Substances

  • Biomarkers
  • Peptides
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases