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).
【저자키워드】 viral infection, structural biology, Protein sequence analyses, 【초록키워드】 COVID-19, Infectious diseases, Epidemiology, SARS-COV-2 infection, Emerging infectious diseases, Infection, Infectious disease, RT-PCR, database, diagnostics, ELISA, Spike protein, Antigen, Computational methods, Spread, Protein, sensitivity, specificity, Epitopes, Receptor-binding domain, pathogen, Sensitivity and specificity, sera, Rapid, plasma, B-cell epitope, nucleoprotein, epitope, predict, SARS-CoV-2 proteins, fragment of, Candidates, signal-to-noise ratio, sequence, help, mixing, disagreement, SARS-CoV-2 protein, N-terminal, noise ratio, Inconclusive, serodiagnostic, FIVE, Result, highest, conducted, the spike protein, the receptor-binding domain, accelerate, ELISA plate, patients with SARS-CoV-2, 【제목키워드】 SARS-CoV-2, B-cell epitope, serological, diagnosis of COVID-19,