Accurately and swiftly identifying SARS-CoV-2 variants is crucial in effective surveillance and disease monitoring. Patients experiencing long COVID may also retain spike protein remnants in their bloodstream.
Image Credit: PHOTOCREO Michal Bednarek/Shutterstock
Protein sequencing makes it possible to differentiate variants in long COVID patients, potentially leading to new insights and treatment strategies for the disease.1
In this article, a method utilizing Quantum-Si's protein sequencing technology on the Platinum® instrument is presented, enabling the distinction of the Alpha, Delta, and Omicron variants based on dissimilarities in the amino acid sequence of their Spike proteins.
Since its discovery in December 2019, the SARS-CoV-2 virus has swiftly spread worldwide, resulting in millions of illnesses and deaths. The appearance of novel variations has raised questions regarding the efficacy of existing countermeasures.2,3
The World Health Organization (WHO) has identified three dominant variants of concern, Alpha, Delta, and Omicron, because of their higher transmission rates and likelihood of causing severe diseases.
These variants exhibit distinct mutations in their genetic sequence, leading to variations in their characteristics and behavior. Quantum-Si offers an accessible protein sequencing technology that can identify the unique protein sequences of a virus and differentiate between different variants.
The technology relies on recognizing individual N-terminal amino acids (NAAs) using various NAA recognizers, followed by sequential cleavage of NAAs with aminopeptidases.
The information-rich output obtained from protein sequencing enables the detection of differences among protein variants, including single amino acid variations in peptide sequences and the presence or absence of specific peptides during infection and in long COVID patients with residual viral proteins.
This distinguishing feature makes the platform highly effective in detecting various protein-level changes resulting from genetic differences among variant viral strains.
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References and further reading
- Cheung C.C.L. et al. (2022) Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19 Gut; 71:226-229.
- Bernal, J. L. et al. (2021) Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N. Engl. J. Med. 385, 585–594.
- Andrews, N. et al. (2022) Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N. Engl. J. Med. 386, 1532–1546.
- Reed, B. D. et al. (2022) Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device. Science 378, 189–192.
About Quantum-SI
Inspired by Ion Torrent’s success at shrinking next-generation sequencing technology into a benchtop instrument, Jonathan Rothberg founded Quantum-Si™ to bring the same semiconductor technology to protein sequencing with the launch of the Platinum® Next-Generation Protein Sequencer™.
That was in Guilford, CT, back in 2013. Fast forward to today and we now have over 1,000 patents issued and applications pending, plus a groundbreaking single-molecule protein sequencing technology platform, the Platinum.
Along the way, we solved critical challenges around sensitive and unambiguous amino acid detection, blending biology, chemistry, and semiconductor technology to help biologists see what other approaches cannot deliver. We also set the stage for a revolution in how scientists understand biology and build new treatments for disease by making single molecule protein sequencing accessible to every lab everywhere.
We are now entering a new phase of our development as a company. Starting with an initial public offering in June 2021 (QSI on the NASDAQ) and continuing with a new product development and operations facility in San Diego, CA, in 2022, we have entered a period of rapid growth. Through this expansion, we will be able to fuel a new era of biology, the post-genomic era, where biologists accelerate basic scientific insight and biomedical advances through the power of next-generation protein sequencing.
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