Saleki Kiarash, Alijanizadeh Parsa, Azadmehr Abbas
Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Department of e-Learning, Virtual School of Medical Education and Management, Shahid Beheshti University of Medical Sciences(SBMU), Tehran, Iran; USERN Office, Babol University of Medical Sciences, Babol, Iran.
Student Research Committee, Babol University of Medical Sciences, Babol, Iran; USERN Office, Babol University of Medical Sciences, Babol, Iran.
Biomed Pharmacother. 2023 Nov;167:115558. doi: 10.1016/j.biopha.2023.115558. Epub 2023 Sep 23.
A major immunopathological feature of Coronavirus disease-2019 (COVID-19) is excessive inflammation in the form of "cytokine storm". The storm is characterized by injurious levels of cytokines which form a complicated network damaging different organs, including the lungs and the brain. The main starter of "cytokine network" hyperactivation in COVID-19 has not been discovered yet. Neuropilins (NRPs) are transmembrane proteins that act as neuronal guidance and angiogenesis modulators. The crucial function of NRPs in forming the nervous and vascular systems has been well-studied. NRP1 and NRP2 are the two identified homologs of NRP. NRP1 has been shown as a viral entry pathway for SARS-CoV2, which facilitates neuroinvasion by the virus within the central or peripheral nervous systems. These molecules directly interact with various COVID-19-related molecules, such as specific regions of the spike protein (major immune element of SARS-CoV2), vascular endothelial growth factor (VEGF) receptors, VEGFR1/2, and ANGPTL4 (regulator of vessel permeability and integrity). NRPs mainly play a role in hyperinflammatory injury of the CNS and lungs, and also the liver, kidney, pancreas, and heart in COVID-19 patients. New findings have suggested NRPs good candidates for pharmacotherapy of COVID-19. However, therapeutic targeting of NRP1 in COVID-19 is still in the preclinical phase. This review presents the implications of NRP1 in multi-organ inflammation-induced injury by SARS-CoV2 and provides insights for NRP1-targeting treatments for COVID-19 patients.
2019冠状病毒病（COVID-19）的一个主要免疫病理特征是以“细胞因子风暴”形式出现的过度炎症。这种风暴的特征是细胞因子水平达到有害程度，形成一个复杂的网络，损害包括肺和脑在内的不同器官。COVID-19中“细胞因子网络”过度激活的主要启动因素尚未被发现。神经纤毛蛋白（NRPs）是跨膜蛋白，充当神经元导向和血管生成调节剂。NRPs在形成神经和血管系统中的关键功能已得到充分研究。NRP1和NRP2是已确定的NRP的两个同系物。NRP1已被证明是严重急性呼吸综合征冠状病毒2（SARS-CoV2）的病毒进入途径，它促进病毒在中枢或外周神经系统内的神经侵袭。这些分子直接与各种COVID-19相关分子相互作用，如刺突蛋白（SARS-CoV2的主要免疫元件）的特定区域、血管内皮生长因子（VEGF）受体VEGFR1/2和血管生成素样蛋白4（血管通透性和完整性调节剂）。NRPs主要在COVID-19患者的中枢神经系统、肺以及肝脏、肾脏、胰腺和心脏的过度炎症损伤中起作用。新发现表明NRPs是COVID-19药物治疗的良好候选者。然而，针对COVID-19中NRP1的治疗仍处于临床前阶段。本综述介绍了NRP1在SARS-CoV2引起的多器官炎症性损伤中的意义，并为COVID-19患者的NRP1靶向治疗提供了见解。
