Protein-based lateral flow assays for COVID-19 detection

Abstract

To combat the enduring and dangerous spread of COVID-19, many innovations to rapid diagnostics have been developed based on proteinprotein interactions of the SARS-CoV-2 spike and nucleocapsid proteins to increase testing accessibility. These antigen tests have most prominently been developed using the lateral flow assay (LFA) test platform which has the benefit of administration at point-of-care, delivering quick results, lower cost, and does not require skilled personnel. However, they have gained criticism for an inferior sensitivity. In the last year, much attention has been given to creating a rapid LFA test for detection of COVID-19 antigens that can address its high limit of detection while retaining the advantages of rapid antibodyantigen interaction. In this review, a summary of these proteinprotein interactions as well as the challenges, benefits, and recent improvements to protein based LFA for detection of COVID-19 are discussed.

Keywords: antibody test; antigen test; covid-19; diagnostics; lateral flow assay.

Fig. 1

SARS-CoV-2 virus and Spike (S) protein structure. (A) Schematic of SARS-CoV-2 virus and its proteins, bound to ACE2 receptor. Reproduced with permission (Kilic et al. (2020)). (B) Schematic of SARS-CoV-2 genome colored by domain. Domains consist of signal sequence (SS), N-terminal domain (NTD), receptor-binding domain (RBD), subdomain 1–2 (SD1–2), S2’ protease cleavage site, fusion peptide (FP), heptad repeat 1–2 (HR1–2), central helix (CH), connector domain (CD), transmembrane domain (TM) and cytoplasmic tail (CT). Reproduced with permission (Wrapp et al. (2020)). (C) Lifecycle of coronavirus from binding to ACE2 and cell entry to synthesis and assembly of viral proteins. Reproduced with permission (Huang et al. 2020).

Fig. 2

(A, B) Schematic representation of LFA testing for SARS-CoV-2 at sample application and at test results. (C) Timeline of expected use of various testing methods for SARS-CoV-2 for accurate detection after exposure to SARS-CoV-2.