Nucleoprotein Proteins

Nucleoprotein Background

A new coronavirus, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), has recently emerged to cause a human pandemic ^[2]. About 2 to 14 days after exposure, the COVID-19 patients mainly manifest fever, cough, shortness of breath or difficulty breathing, chills, accompanied by severe pulmonary infection. After the virus is sequenced, nucleic acid tests have been used to detect SARS-CoV-2 infection. Nasopharyngeal swab nucleic acid tests detect viral RNA and indicate current viral infection, and they are an essential part of contact tracing and testing ^[3]. However, they are far not to meet the huge demand for the PCR primers and global supply challenges. Berend-Jan Bosch, a coronavirus specialist at Utrecht University in the Netherlands, said that all viral proteins will elicit antibody responses to some extent. And Peng Zhou, who leads the bat virus infection and immunity group at the Wuhan Institute of Virology in China, said that since the nucleocapsid protein is the most abundant viral protein, it's easy to detect. But spike protein is very specific for the new coronaviruses. In response to the viral proteins, the immune system triggers the production of antibodies that flag or neutralize the virus. So neutralizing antibodies of spike protein and nucleocapsid can be an indicator for the SARS-CoV-2. Based on these factors, scientific researchers developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Package of the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) forms the nucleocapsid of the SARS-CoV-2. People commonly call it N protein. The nucleocapsid is a structural protein complexed with genomic RNA, and it interacts with the viral membrane protein during virion assembly. N protein is important in enhancing the efficiency of virus transcription and assembly ^[1]. Coronavirus N proteins have three distinct and highly conserved domains: the N terminal domain (NTD/domain 1) and the C-terminal domain (CTD/domain 3), which are separated by an intrinsically disordered central region (RNA-binding domain/domain 2) ^[1]. Besides, N protein plays a crucial role in viral pathogenesis. Theoretically, the viral antigen is the specific marker of the virus and appears before the corresponding antibody within the contracted population. Some experiments have demonstrated that nucleocapsid protein can indicate the presence of COVID-19.

[1] Ruth McBride, Marjorie van Zyl, et al. The Coronavirus Nucleocapsid Is a Multifunctional Protein [J]. Viruses. 2014 Aug; 6(8): 2991–3018.
[2] Zhou P, Yang XL, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-3.
[3] Corman VM, Landt O, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro surveillance : bulletin Europeen sur les maladies transmissibles European communicable disease bulletin. 2020 Jan;25(3):2000045.