MALDI-TOF Mass Spectrometric Detection of SARS-CoV-2 Using Cellulose Sulfate Ester Enrichment and Hot Acid Treatment

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here we report a novel strategy for the rapid detection of SARS-CoV-2 based on an enrichment approach exploiting the affinity between the virus and cellulose sulfate ester functional groups, hot acid hydrolysis, and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Virus samples were enriched using cellulose sulfate ester microcolumns. Virus peptides were prepared using the hot acid aspartate-selective hydrolysis and characterized by MALDI-TOF MS. Collected spectra were processed with a peptide fingerprint algorithm, and searching parameters were optimized for the detection of SARS-CoV-2. These peptides provide high sequence coverage for nucleocapsid (N protein) and allow confident identification of SARS-CoV-2. Peptide markers contributing to the detection were rigorously identified using bottom-up proteomics. The approach demonstrated in this study holds the potential for developing a rapid assay for COVID-19 diagnosis and detecting virus variants from a variety of sources, such as sewage and nasal swabs.

Mechanisms, Techniques and Devises of Airborne Virus Detection: A Review

“…As a result, mass spectrometry can accurately detect the molecular weight and purity of biological macromolecules such as polypeptides, proteins, nucleic acids and polysaccharides with high accuracy. Virus detection is now being done using liquid chromatography mass spectrometry, electrospray mass spectrometry, and Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) [123][124][125][126][127]. Many assays have been developed on a chip as modern detection techniques become more miniaturized and portable.…”

The Application of Biomaterials for the Vaccine, Treatment, and Detection of SARS-CoV-2

“…172 Cellulose and alginate have also been explored as drug delivery vehicles for anti-SARS-CoV-2 agents, with promising results in vitro and in animal models. 173,174 2.2.3. Lipid Biomaterials in the Treatment of SARS-CoV-2 and Drug Delivery Systems.…”

Algorithms push forward the application of MALDI–TOF mass fingerprinting in rapid precise diagnosis

“…Rapid 88 with diagnosis accuracy reaching 85%-98%. We have also used the approach for melanoma-type skin cancer analysis by direct mass fingerprinting of blood circulating exosomes 85 and skin surface cells collected on adhesive tapes.…”

“…Through the combination of appropriate sampling methods, sample pretreatment procedures, and data learning algorithms, MALDI–TOF mass fingerprinting has been used for rapid and noninvasive diagnosis for broad types of diseases. For instance, it has shown satisfying performance in COVID‐19 diagnosis, by direct mass fingerprinting of nasal swabs, 86 blood serum, 51 saliva 87 as well as the virus peptides enriched from those samples, 88 with diagnosis accuracy reaching 85%–98%. We have also used the approach for melanoma‐type skin cancer analysis by direct mass fingerprinting of blood circulating exosomes 85 and skin surface cells collected on adhesive tapes 52 .…”