Discriminative Identification of SARS-CoV-2 Variants Based on Mass-Spectrometry Analysis
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ABSTRACT:
SUBMITTER: Feldberg L
PROVIDER: S-EPMC10525290 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Mass mapping using high-resolution mass spectrometry has been applied to identify and rapidly distinguish SARS-CoV-2 coronavirus strains across five major variants of concern. Deletions or mutations within the surface spike protein across these variants, which originated in the UK, South Africa, Brazil and India (known as the alpha, beta, gamma and delta variants respectively), lead to associated mass differences in the mass maps. Peptides of unique mass have thus been determined that can be used to identify and distinguish the variants. The same mass map profiles are also utilized to construct phylogenetic trees, without the need for protein (or gene) sequences or their alignment, in order to chart and study viral evolution. The combined strategy offers advantages over conventional PCR-based gene-based approaches exploiting the ease with which protein mass maps can be generated and the speed and sensitivity of mass spectrometric analysis.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the on-going global pandemic of coronavirus disease 2019 (COVID-19) that continues to pose a significant threat to public health worldwide. SARS-CoV-2 encodes four structural proteins namely membrane, nucleocapsid, spike, and envelope proteins that play essential roles in viral entry, fusion, and attachment to the host cell. Extensively glycosylated spike protein efficiently binds to the host angiotensin-converting enzyme 2 initiating viral entry and pathogenesis. Reverse transcriptase polymerase chain reaction on nasopharyngeal swab is the preferred method of sample collection and viral detection because it is a rapid, specific, and high-throughput technique. Alternate strategies such as proteomics and glycoproteomics-based mass spectrometry enable a more detailed and holistic view of the viral proteins and host-pathogen interactions and help in detection of potential disease markers. In this review, we highlight the use of mass spectrometry methods to profile the SARS-CoV-2 proteome from clinical nasopharyngeal swab samples. We also highlight the necessity for a comprehensive glycoproteomics mapping of SARS-CoV-2 from biological complex matrices to identify potential COVID-19 markers.
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Project description:ObjectiveThe rapid detection and differentiation of strains of the BA.2.86 lineage including the new sub-variant JN.1 (BA.2.86.1.1) is demonstrated employing selected ion monitoring (SIM) and high resolution mass spectrometry.MethodsA study of a preliminary set of BA.2.86 lineage positive specimens, identified BA.2.86 and BA.2.86.1.1 peptide markers in 62.5 % and 29.1 % of samples.ResultsPeptide-specific markers in the surface spike protein associated with the L455S mutation are confidently detected with high sensitivity in protein and virus digests.The virus was thus confidently assigned in over 91 % of positive specimens.ConclusionsA rise in the global prevalence of the JN.1 (BA.2.86.1.1) immune evasive sub-variant, that emerged in late 2023, requires that new strategies and protocols to detect such strains in human specimens are accelerated and implemented.
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