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SARS-CoV-2: The Self-Nonself Issue and Diagnostic Tests.

Darja Kanduc1

  • 1Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Bari, Italy.

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|April 17, 2023
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Summary
This summary is machine-generated.

Molecular analysis reveals significant sequence overlap between SARS-CoV-2 spike protein and human proteins. This overlap in peptide and genetic sequences may explain false positives in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests.

Keywords:
PCR testsSARS-CoV-2 spike gpfalse positivesself-nonselfserological tests

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Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) report inaccuracies, including false negatives and positives.
  • The molecular basis for these diagnostic unreliabilities requires investigation.

Purpose of the Study:

  • To determine the specificity of sequences used in serological and polymerase chain reaction (PCR) tests for SARS-CoV-2 detection.
  • To investigate the molecular basis of potential unreliability in SARS-CoV-2 diagnostics.

Main Methods:

  • Analysis of the SARS-CoV-2 spike glycoprotein (gp) sequences.
  • Utilized Uniprot database's Peptide Search to analyze peptide sequence sharing between the spike antigen and the human proteome.
  • Employed NCBI's nucleotide Basic Local Alignment Search Tool (BLASTn) to investigate oligonucleotide sequence sharing.

Main Results:

  • Identified extensive pentapeptide sequence sharing between the SARS-CoV-2 spike gp and the human proteome.
  • Found only 107 unique pentapeptides in the SARS-CoV-2 spike gp compared to the human proteome.
  • Demonstrated that nucleotide sequences coding for these unique pentapeptides are largely present in human nucleic acids, indicating minimal genetic distinction.

Conclusions:

  • The findings have significant immunological implications regarding viral versus human specificity.
  • The substantial sequence homology likely explains the occurrence of false positives in both serological and PCR-based SARS-CoV-2 diagnostic tests.