Enhancing Diagnostic Sensitivity: Investigating Molecular Mechanisms of Antigen Rapid Diagnostic Test (AgRDTs) Variability Across SARS-CoV-2 Variants

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Abstract

The emergence of COVID-19, caused by SARS-CoV-2, led to the widespread use of antigen rapid diagnostic tests (AgRDTs) due to their speed, affordability, and ease of use. However, the diagnostic sensitivity of AgRDTs has been inconsistent across emerging SARS-CoV-2 variants, with some variants exhibiting reduced detection rates. Thus, AgRDTs have been unreliable in detecting the different variants of SARS-CoV-2. This study explores the molecular mechanisms responsible for this variability, focusing on structural changes in the viral spike (S) and nucleocapsid (N) proteins and how these changes affect antigen-antibody interactions. Using structural biology techniques such as X-ray crystallography and cryo-electron microscopy, molecular virology approaches like whole genome sequencing, immunoassays including ELISA and surface plasmon resonance (SPR), and computational modelling tools for molecular dynamics simulations, this research will uncover specific mutations that impact diagnostic sensitivity. The results of this study will inform the development of next-generation AgRDTs with enhanced sensitivity across diverse viral variants, thereby supporting global efforts in pandemic surveillance and control.
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Preprint ARPHA Preprints https://doi.org/10.3897/arphapreprints.e152096 (06 Mar 2025) https://doi.org/10.3897/arphapreprints.e152096 (06 Mar 2025) Published in: Research Ideas and Outcomes https://doi.org/10.3897/rio.11.e152094 Other versions: - Preprint InfoPreprint Info - CiteCite - MetricsMetrics - CommentComment - RelatedRelated - CitedCited ARPHA Preprints doi: 10.3897/arphapreprints.e152096 First posted 06 Mar 2025 Authors Frank Twum Twum Aboagye - Corresponding author Biomedical and Public Health Research Unit, CSIR-Water Research Institute, Accra, Ghana The Graduate School, Augusta University, Georgia, United States of America West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana Biomedical and Public Health Research Unit, CSIR-Water Research Institute, Accra, Ghana Biomedical and Public Health Research Unit, CSIR-Water Research Institute, Accra, Ghana Department of Genetics and Biochemistry, Clemson University, South Carolina, United States of America Biomedical and Public Health Research Unit, CSIR-Water Research Institute, Accra, Ghana Biomedical and Public Health Research Unit, CSIR-Water Research Institute, Accra, Ghana Roche Product Ghana Limited, Accra, Ghana Yvonne A. Ashong - Corresponding author Department of Parasitology, Noguchi Memorial Institute of Medical Research, Accra, Ghana Conflict of interest The authors have declared that no competing interests exist. This is an open access preprint distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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