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

• Published in: Angewandte Chemie Vol. 134; no. 9
• Main Authors: Jin, Zhicheng, Mantri, Yash, Retout, Maurice, Cheng, Yong, Zhou, Jiajing, Jorns, Alec, Fajtova, Pavla, Yim, Wonjun, Moore, Colman, Xu, Ming, Creyer, Matthew N., Borum, Raina M., Zhou, Jingcheng, Wu, Zhuohong, He, Tengyu, Penny, William F., O'Donoghue, Anthony J., Jokerst, Jesse V.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 21-02-2022
• Subjects: Chemistry; Colloids; Colorimetric analysis; Coronaviruses; COVID-19; Life cycles; mpro/3clpro/nsp5; Nanoparticles; Nucleic acids; Pandemics; Peptides; Portable equipment; Protease; Proteinase; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Smart mask; Substrates; Viral diseases; Zwitterionic peptide; Zwitterions
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202112995

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.
A rapid colorimetric detection of SARS‐CoV‐2 protease using a zwitterionic peptide and gold colloids is reported. The sensor showed good performance in exhaled breath condensate with a limit of detection in the low nanomolar range. This technology can be integrated into regular face coverings for COVID‐detection.