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. 2020 Nov 25;6(11):2046-2052.
doi: 10.1021/acscentsci.0c00855. Epub 2020 Sep 23.

The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device

Alexander N Baker  1 , Sarah-Jane Richards  1 , Collette S Guy  1   2 , Thomas R Congdon  1 , Muhammad Hasan  1 , Alexander J Zwetsloot  3 , Angelo Gallo  1 , Józef R Lewandowski  1 , Phillip J Stansfeld  1   2 , Anne Straube  3 , Marc Walker  4 , Simona Chessa  5 , Giulia Pergolizzi  5 , Simone Dedola  5 , Robert A Field  5   6 , Matthew I Gibson  1   3
Affiliations

The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device

Alexander N Baker et al. ACS Cent Sci. .

Erratum in

Abstract

There is an urgent need to understand the behavior of the novel coronavirus (SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that N-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in under 30 min, showing the potential of this system as a low-cost detection platform.

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Conflict of interest statement

The authors declare the following competing financial interest(s): M.I.G., A.N.B., and S.J.R. are named inventors of a patent relating to this work. R.F. is a shareholder in Iceni diagnostics who part-funded this work.

Figures

Figure 1
Figure 1
(A) Sequence alignment between the S1 domains of the SARS-COV-2 and MERS spike proteins. Regions important for sialic acid binding are highlighted by red boxes; (B) Model showing the hypothesized sialic acid binding sites (yellow CPK coloring) for the SARS-COV-2 spike protein trimer; (C) A comparison between the sialic acid binding sites from MERS (PDB entry 6Q04) and the SARS-COV-2 model (PDB entry 6VSB) in complex with a2,3′-sialyllactose.
Figure 2
Figure 2
Design concept for glyco-lateral flow devices. (A) Lateral flow assay for virus, using glycan capture units; (B) Synthetic procedure for glyconanoparticles.
Figure 3
Figure 3
Biolayer interferometry analysis of SARS-COV-2 spike protein with glyconanoparticles. (A) Screening using PHEA50@AuNP35 at OD = 1; Dose-dependent binding of NeuNAc-PHEA50 using (B) @AuNP16 and (C) @AuNP35. OD = 1 (−), 0.5(-), 0.25(-), 0.125(-); (D) Binding curves.
Figure 4
Figure 4
Half lateral flow analysis of NeuNAcPHEAx@AuNPy particles. (A) Half lateral flow assay setup with target protein immobilized on the test line; (B) Effect of polymer chain length and particle size on lateral flow binding; (C) Signal:noise analysis; (D) Selectivity of NeuNAcPHEA50@AuNP35 against a panel of lectins (inset example LFD strips). (E) Selectivity of NeuNAcPHEA50@AuNP35 against S1 protein from different coronavirus strains. Data is the mean from 3 repeats. Original LFD strips are in the SI. Test lines are within the dashed-line box. 2,3′SL-BSA = 2,3′-sialyllactose-functionalized BSA.
Figure 5
Figure 5
(A) Detection limit analysis of galactose or NeuNAc functionalized AuNPs against immobilized SARS-COV-2,S1 using “half LFD” assays; (B) Signal intensity analysis; (C) Dipstick lateral flow tests using NeuNAcPHEA50@AuNP35 and BSA-NeuNAc as the test line and RCA120 as the control line. PS-NP = 100 nm polystyrene colloid, or + SARS-COV-2,S1. N/A is with no polystyrene analyte. (D) Half lateral flow analysis of SARS-COV-2 Spike pseudotyped lentivirus against NeuNAcPHEA50@AuNP35 or GalPHEA50@AuNP35 nanoparticles. In each image, the test line region is indicated by the dashed box. Complete original images are in Supporting Information.
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