TY - JOUR

T1 - Structural Features of Nucleoproteins from the Recently Discovered Orthonairovirus songlingense and Norwavirus beijiense

AU - Yanshin, Alexey O

AU - Ivkina, Daria I

AU - Tuyrin, Vitaliy Yu

AU - Osinkina, Irina A

AU - Tishin, Anton E

AU - Olkin, Sergei E

AU - Ukladov, Egor O

AU - Radchenko, Nikita S

AU - Arkhipov, Sergey G

AU - Ryzhykau, Yury L

AU - Li, Na

AU - Agafonov, Alexander P

AU - Imatdinov, Ilnaz R

AU - Gladysheva, Anastasia V

N1 - This study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2025-452) as part of the implementation of certain activities of the Federal Scientific and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure. Yury L. Ryzhykau acknowledges the Ministry of Science and Higher Education of the Russian Federation (agreement 075-03-2025-662, project FSMG-2025-0003) for the support of his contribution to the design of the small-angle scattering experiment using a concentration series and to the analysis of concentration dependence.

PY - 2025/8/1

Y1 - 2025/8/1

N2 - The recent discovery of Orthonairovirus songlingense (SGLV) and Norwavirus beijiense (BJNV) in China has raised significant concern due to their potential to cause severe human disease. However, little is known about the structural features and function of their nucleoproteins, which play a key role in the viral life cycle. By combining small-angle X-ray scattering (SAXS) data and AlphaFold 3 simulations, we reconstructed the BJNV and SGLV nucleoprotein structures for the first time. The SGLV and BJNV nucleoproteins have structures that are broadly similar to those of Orthonairovirus haemorrhagiae (CCHFV) nucleoproteins despite low sequence similarity. Based on structural analysis, several residues located in the positively charged region of BJNV and SGLV nucleoproteins have been indicated to be important for viral RNA binding. A positively charged RNA-binding crevice runs along the interior of the SGLV and BJNV ribonucleoprotein complex (RNP), shielding the viral RNA. Despite the high structural similarity between SGLV and BJNV nucleoprotein monomers, their RNPs adopt distinct conformations. These findings provide important insights into the molecular mechanisms of viral genome packaging and replication in these emerging pathogens. Also, our work demonstrates that experimental SAXS data can validate and improve predicted AlphaFold 3 structures to reflect their solution structure and also provides the first low-resolution structures of the BJNV and SGLV nucleoproteins for the future development of POC tests, vaccines, and antiviral drugs.

AB - The recent discovery of Orthonairovirus songlingense (SGLV) and Norwavirus beijiense (BJNV) in China has raised significant concern due to their potential to cause severe human disease. However, little is known about the structural features and function of their nucleoproteins, which play a key role in the viral life cycle. By combining small-angle X-ray scattering (SAXS) data and AlphaFold 3 simulations, we reconstructed the BJNV and SGLV nucleoprotein structures for the first time. The SGLV and BJNV nucleoproteins have structures that are broadly similar to those of Orthonairovirus haemorrhagiae (CCHFV) nucleoproteins despite low sequence similarity. Based on structural analysis, several residues located in the positively charged region of BJNV and SGLV nucleoproteins have been indicated to be important for viral RNA binding. A positively charged RNA-binding crevice runs along the interior of the SGLV and BJNV ribonucleoprotein complex (RNP), shielding the viral RNA. Despite the high structural similarity between SGLV and BJNV nucleoprotein monomers, their RNPs adopt distinct conformations. These findings provide important insights into the molecular mechanisms of viral genome packaging and replication in these emerging pathogens. Also, our work demonstrates that experimental SAXS data can validate and improve predicted AlphaFold 3 structures to reflect their solution structure and also provides the first low-resolution structures of the BJNV and SGLV nucleoproteins for the future development of POC tests, vaccines, and antiviral drugs.

UR - https://pubmed.ncbi.nlm.nih.gov/40806574/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105013266429&origin=inward

U2 - 10.3390/ijms26157445

DO - 10.3390/ijms26157445

M3 - Article

C2 - 40806574

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 15

M1 - 7445

ER -