9kur

From Proteopedia

Crystal structure of mAb nCoV400Fab with SARS-CoV-2 N-CTD Complex

Structural highlights

9kur is a 6 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.06Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NCAP_SARS2 Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.

Publication Abstract from PubMed

The transition of SARS-CoV-2 into a recurrent, seasonal pathogen has underscored the need for the induction of durable immune protection. The nucleocapsid (N) protein is regarded as a promising complementary target for therapeutic and vaccine strategies, owing to its structural robustness, clinical relevance, and ability to elicit critical immune response. Within the N protein, the C-terminal domain (N-CTD) plays a pivotal role in assembly of viral RNA (vRNA)-N protein complexes, and in facilitating liquid-liquid phase separation (LLPS) through specific interactions with RNA on its dimerization surface. Despite its functional importance, the molecular mechanisms by which the RNA-binding surface of this domain can be selectively targeted by inhibitors remain poorly defined. Herein, we report a 2.06 A crystal structure of the SARS-CoV-2 N-CTD in complex with nCoV400Fab, a human monoclonal antibody derived from single B-cell screening. The structure reveals that nCoV400Fab engages multiple basic residues on the RNA-binding surface, forming a steric blockade that hinders vRNA binding. Functional assays demonstrate that nCoV400Fab disrupts both viral ribonucleoprotein (vRNP) assembly and RNA-induced condensate formation. Together, these findings define a structural mechanism by which a human antibody disrupts the RNA-binding surface of N-CTD, laying the foundation for the development of macromolecular inhibitors.

Structural basis of a human antibody targeting SARS-CoV-2 nucleocapsid protein dimerization domain and interfering with RNA-binding.,Xue S, He S, Huang Z, Yang M, Hu G, Chen X, Chen Q, Zhou W, Lin S, Chen S Commun Biol. 2025 Aug 19;8(1):1248. doi: 10.1038/s42003-025-08648-x. PMID:40830575^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xue S, He S, Huang Z, Yang M, Hu G, Chen X, Chen Q, Zhou W, Lin S, Chen S. Structural basis of a human antibody targeting SARS-CoV-2 nucleocapsid protein dimerization domain and interfering with RNA-binding. Commun Biol. 2025 Aug 19;8(1):1248. PMID:40830575 doi:10.1038/s42003-025-08648-x