9kn1

From Proteopedia

Crystal structure of SARS-CoV-2 nucleocapsid phosphoprotein N-terminal domain(N-NTD) in complex with UMP

Structural highlights

9kn1 is a 4 chain structure with sequence from 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 2.12Å
Ligands:
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

Human coronaviruses (HCoVs) include common cold viruses such as HCoV-229E, OC43, NL63 and HKU1 as well as MERS-CoV and SARS-CoV, which cause severe respiratory disease. Recently, SARS-CoV-2 caused a COVID-19 pandemic. The nucleocapsid (N) protein of coronaviruses, which is essential for RNA binding and homodimerization, has a highly conserved structure across viruses. Previous studies revealed that compound PJ34 is an inhibitor of nucleic acid binding to the N-terminal domain (NTD) of the HCoV-OC43 N protein, suggesting that it could block viral replication. However, testing with SARS-CoV-2 showed that PJ34 did not inhibit viral replication. Structural analysis suggests that the substitution of Tyr for Ala at position 50 (corresponding to Tyr63 in OC43), may affect the ability to interact with compounds such as PJ34, explaining its lack of efficacy. These findings underscore the importance of structure-based drug development targeting the N protein, which remains an important therapeutic target in all coronaviruses.

Structural insights into nucleocapsid protein variability: Implications for PJ34 efficacy against SARS-CoV-2.,Yamamoto A, Ito H, Sakaguchi T, Higashiura A Virology. 2025 Mar;604:110411. doi: 10.1016/j.virol.2025.110411. Epub 2025 Jan , 17. PMID:39848104^[1]

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

References

↑ Yamamoto A, Ito H, Sakaguchi T, Higashiura A. Structural insights into nucleocapsid protein variability: Implications for PJ34 efficacy against SARS-CoV-2. Virology. 2025 Mar;604:110411. PMID:39848104 doi:10.1016/j.virol.2025.110411