Yanshin Alexey O, Ivkina Daria I, Tuyrin Vitaliy Yu, Osinkina Irina A, Tishin Anton E, Olkin Sergei E, Ukladov Egor O, Radchenko Nikita S, Arkhipov Sergey G, Ryzhykau Yury L, Li Na, Agafonov Alexander P, Imatdinov Ilnaz R, Gladysheva Anastasia V
State Research Center of Virology and Biotechnology "Vector", 630559 Kol'tsovo, Russia.
Physics Department, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2025 Aug 1;26(15):7445. doi: 10.3390/ijms26157445.
The recent discovery of (SGLV) and (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 (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.
近期在中国发现的[具体病毒名称未给出，推测为“SGLV”和“BJNV”]因其可能引发严重人类疾病而引发了重大关注。然而，对于它们核蛋白的结构特征和功能却知之甚少，而核蛋白在病毒生命周期中起着关键作用。通过结合小角X射线散射（SAXS）数据和AlphaFold 3模拟，我们首次重建了BJNV和SGLV核蛋白的结构。尽管序列相似性较低，但SGLV和BJNV核蛋白的结构与[具体病毒名称未给出，推测为“CCHFV”]核蛋白的结构大致相似。基于结构分析，已表明位于BJNV和SGLV核蛋白带正电区域的几个残基对于病毒RNA结合很重要。一个带正电的RNA结合裂隙沿着SGLV和BJNV核糖核蛋白复合体（RNP）的内部延伸，保护病毒RNA。尽管SGLV和BJNV核蛋白单体之间结构高度相似，但它们的RNP呈现出不同的构象。这些发现为这些新兴病原体中病毒基因组包装和复制的分子机制提供了重要见解。此外，我们的工作表明，实验性的SAXS数据可以验证和改进预测的AlphaFold 3结构以反映其溶液结构，并且还为即时检测（POC）测试、疫苗和抗病毒药物的未来开发提供了BJNV和SGLV核蛋白的首个低分辨率结构。
