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Abstract
Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N = 80 samples from persons with RT-PCR confirmed SARS-CoV-2 infection), and a specificity of 97.2% (N = 106 control samples).
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1 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); Seattle Children’s Research Institute, Center for Global Infectious Disease Research, Seattle, USA (GRID:grid.240741.4) (ISNI:0000 0000 9026 4165)
2 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); University of Washington, Department of Biochemistry, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Institute for Protein Design (IPD), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Howard Hughes Medical Institute, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
3 University of Washington, Department of Biochemistry, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Institute for Protein Design (IPD), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
4 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); University of Washington, Department of Biochemistry, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Institute for Protein Design (IPD), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
5 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); University of Washington, Division of Allergy and Infectious Diseases, Department of Medicine, Center for Emerging and Re-Emerging Infectious Diseases (CERID), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
6 Seattle Children’s Research Institute, Center for Global Infectious Disease Research, Seattle, USA (GRID:grid.240741.4) (ISNI:0000 0000 9026 4165); University of Washington, Department of Pediatrics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
7 University of Washington, Division of Allergy and Infectious Diseases, Department of Medicine, Center for Emerging and Re-Emerging Infectious Diseases (CERID), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Laboratory Medicine and Pathology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Benaroya Research Institute, Seattle, USA (GRID:grid.416879.5) (ISNI:0000 0001 2219 0587); University of Washington, Department of Global Health, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
8 University of Washington, Division of Allergy and Infectious Diseases, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Laboratory Medicine and Pathology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Department of Epidemiology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
9 University of Washington, Department of Biochemistry, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
10 University of Washington, Division of Allergy and Infectious Diseases, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622)
11 University of Washington, Department of Pharmaceutics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
12 University of Washington, Department of Laboratory Medicine and Pathology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
13 University of Washington, Division of Allergy and Infectious Diseases, Department of Medicine, Center for Emerging and Re-Emerging Infectious Diseases (CERID), Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
14 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); Seattle Children’s Research Institute, Center for Global Infectious Disease Research, Seattle, USA (GRID:grid.240741.4) (ISNI:0000 0000 9026 4165); University of Washington, Department of Medical Education and Biomedical Informatics & Department of Global Health, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
15 Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); University of Washington, Howard Hughes Medical Institute, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Department of Microbiology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Department of Global Health, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)