Eltayeb Ahmed, Adilović Muhamed, Golzardi Maryam, Hromić-Jahjefendić Altijana, Rubio-Casillas Alberto, Uversky Vladimir N, Redwan Elrashdy M
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
PeerJ. 2025 May 20;13:e19429. doi: 10.7717/peerj.19429. eCollection 2025.
COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）给全球健康带来了重大挑战。其发病机制中的一个关键因素是核衣壳蛋白（NP），它对病毒复制和组装至关重要。虽然已知来自其他冠状病毒（如SARS-CoV和MERS-CoV）的核衣壳蛋白会增加炎症并导致急性肺损伤，但SARS-CoV-2核衣壳蛋白对宿主细胞的具体影响在很大程度上仍未得到探索。最近的研究结果表明，核衣壳蛋白作为一种病原体相关分子模式（PAMP），与Toll样受体2（TLR2）结合，激活核因子κB（NF-κB，活化B细胞的轻链增强子核因子）和丝裂原活化蛋白激酶（MAPK）信号通路。这种激活在重症COVID-19病例中尤为明显，导致可溶性细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）水平升高，这会导致内皮功能障碍和多器官损伤。此外，核衣壳蛋白与炎症过度和血栓形成有关，这是COVID-19严重程度和长期后遗症的关键因素。它与甘露聚糖结合凝集素丝氨酸蛋白酶2（MASP-2）结合的可能性也可能与长期COVID患者的持续症状有关。了解这些机制，特别是核衣壳蛋白在血栓形成中的作用，对于开发针对性疗法以有效管理COVID-19的急性和慢性影响至关重要。这篇综述旨在阐明核衣壳蛋白的多方面作用，强调其对病毒发病机制、免疫逃逸和血栓形成事件加剧的贡献，从而为减轻COVID-19的严重和长期影响的潜在治疗靶点提供见解。
