Structural Basis for SARS-CoV-2 Nucleocapsid Protein Recognition by Single-Domain Antibodies
Open Access
- 26 July 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 12, 719037
- https://doi.org/10.3389/fimmu.2021.719037
Abstract
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is the most severe public health event of the twenty-first century. While effective vaccines against SARS-CoV-2 have been developed, there remains an urgent need for diagnostics to quickly and accurately detect infections. Antigen tests, particularly those that detect the abundant SARS-CoV-2 Nucleocapsid protein, are a proven method for detecting active SARS-CoV-2 infections. Here we report high-resolution crystal structures of three llama-derived single-domain antibodies that bind the SARS-CoV-2 Nucleocapsid protein with high affinity. Each antibody recognizes a specific folded domain of the protein, with two antibodies recognizing the N-terminal RNA binding domain and one recognizing the C-terminal dimerization domain. The two antibodies that recognize the RNA binding domain affect both RNA binding affinity and RNA-mediated phase separation of the Nucleocapsid protein. All three antibodies recognize highly conserved surfaces on the Nucleocapsid protein, suggesting that they could be used to develop affordable diagnostic tests to detect all circulating SARS-CoV-2 variants.Keywords
Funding Information
- National Institute of General Medical Sciences
This publication has 31 references indexed in Scilit:
- How good are my data and what is the resolution?Acta Crystallographica Section D-Biological Crystallography, 2013
- An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmissionHepatology, 2013
- NIH Image to ImageJ: 25 years of image analysisNature Methods, 2012
- Towards automated crystallographic structure refinement with phenix.refineActa Crystallographica Section D-Biological Crystallography, 2012
- Overview of theCCP4 suite and current developmentsActa Crystallographica Section D-Biological Crystallography, 2011
- Features and development of CootActa Crystallographica Section D-Biological Crystallography, 2010
- XDSActa Crystallographica Section D-Biological Crystallography, 2010
- Expression and Purification of Soluble His6-Tagged TEV ProteasePublished by Springer Science and Business Media LLC ,2009
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007
- Nucleocapsid Protein as Early Diagnostic Marker for SARSEmerging Infectious Diseases, 2004