Comput Biol Med . High-specificity targets in SARS-CoV-2 N protein for serological detection and distinction from SARS-CoV

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Comput Biol Med


. 2022 Jan 29;143:105272.
doi: 10.1016/j.compbiomed.2022.105272. Online ahead of print.
High-specificity targets in SARS-CoV-2 N protein for serological detection and distinction from SARS-CoV


Jianhai Yu ¹ , Zhiran Qin ² , Xuling Liu ³ , Xiaoen He ⁴ , Jinxiu Yao ⁵ , Xuan Zhou ⁶ , Kun Wen ⁷ , Nan Yu ⁸ , Qinghua Wu ⁹ , Weiwei Xiao ¹⁰ , Li Zhu ¹¹ , Chengsong Wan ¹² , Bao Zhang ¹³ , Wei Zhao ¹⁴



Affiliations

• PMID: 35121361
• DOI: 10.1016/j.compbiomed.2022.105272

Abstract

Numerous serological detection kits are being rapidly developed and approved for screening and diagnosing suspected coronavirus disease 2019 (COVID-19) cases. However, cross-reactivity between pre-existing antibodies against other coronaviruses and the captured antigens in these kits can affect detection accuracy, emphasizing the necessity for identifying highly specific antigen fragments for antibody detection. Thus, we performed a conservation and specificity analysis of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein. We also integrated various B-cell epitope prediction methods to obtain possible dominant epitope regions for the N protein, analyzed the differences in serological antibody levels for different epitopes using ELISA, and identified N protein epitopes for IgG and IgM with high-specificity. The SARS-CoV-2 N protein showed low mutation rates and shared the highest amino acid similarity with SARS-CoV; however, it differed substantially from other coronaviruses. Tests targeting the SARS-CoV-2 N protein produce strong positive results in patients recovering from SARS-CoV. The N18-39 and N183-197 epitopes for IgG and IgM detection, respectively, can effectively overcome cross-reactivity, and even exhibit good specificity between SARS-CoV-2 and SARS-CoV. The antibody levels detected with these were consistent with those detected using the complete N protein. These findings provide a basis for serological diagnosis and determining the kinetics of SARS-CoV-2 antibody detection in patients.

Keywords: Cross-reactivity; Epitope; N protein; Novel coronavirus (SARS-CoV-2); Serological detection.