ARPHA Preprints, doi: 10.3897/arphapreprints.e152096
Enhancing Diagnostic Sensitivity: Investigating Molecular Mechanisms of Antigen Rapid Diagnostic Test (AgRDTs) Variability Across SARS-CoV-2 Variants
expand article infoFrank Twum Twum Aboagye‡, Mawutor Kwame Ahiabu§, Maame Ekua Acquah|, Queenstar Naa Dedei Quarshie‡, Naa Adjeley Kumah‡, Hannah Segbefiah Akahoho, Nfayem Imoro‡, Abena Konadu Owusu-Senyah Enninful‡, Bill Clinton Egyam#, Yvonne A. Ashong¤
‡ 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¶ Department of Genetics and Biochemistry, Clemson University, South Carolina, United States of America# Roche Product Ghana Limited, Accra, Ghana¤ Department of Parasitology, Noguchi Memorial Institute of Medical Research, Accra, Ghana

Corresponding author: Frank Twum Aboagye ( frankaboagye71@gmail.com )

Corresponding author: Yvonne Ashong ( yashong@noguchi.ug.edu.gh )

© Frank Twum Aboagye, Mawutor Kwame Ahiabu, Maame Ekua Acquah, Queenstar Quarshie, Naa Kumah, Hannah Akahoho, Nfayem Imoro, Abena Enninful, Bill Egyam, Yvonne Ashong.
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.
Citation: Aboagye FT, Ahiabu MK, Acquah ME, Quarshie QD, Kumah N, Akahoho H, Imoro N, Enninful AO-S, Egyam B, Ashong YA (2025) Enhancing Diagnostic Sensitivity: Investigating Molecular Mechanisms of Antigen Rapid Diagnostic Test (AgRDTs) Variability Across SARS-CoV-2 Variants. ARPHA Preprints. https://doi.org/10.3897/arphapreprints.e152096
Open Access
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.

Keywords
Antigen Rapid Diagnostic Tests (AgRDTs), SARS-CoV-2 Variants, Diagnostic Sensitivity Variability, Molecular Mechanisms, Structural Biology