Al-Thomali Asma W, Al-Kuraishy Hayder M, Al-Gareeb Ali I, K Al-Buhadiliy Ali, De Waard Michel, Sabatier Jean-Marc, Khan Khalil Atif Ali, Saad Hebatallah M, Batiha Gaber El-Saber
Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, MBChB, MRCP, FRCP, Baghdad P.O. Box 14132, Iraq.
Biomedicines. 2022 Aug 20;10(8):2032. doi: 10.3390/biomedicines10082032.
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood-brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染可引发适应性和先天性免疫反应，导致不受控制的炎症反应以及相关的局部和全身组织损伤，同时还会引发血栓栓塞性疾病，这可能会增加COVID-19患者发生急性缺血性卒中（AIS）的风险。神经纤毛蛋白（NRP-1）作为血管内皮生长因子（VEGF）、整合素和丛蛋白的共受体，参与了AIS的发病机制。NRP-1也被视为SARS-CoV-2进入细胞的共受体，并促进其通过嗅觉上皮进入大脑。NRP-1被认为是SARS-CoV-2与血管紧张素转换酶2（ACE2）结合的辅助因子，因为即使存在NRP-1，ACE2的缺失也会降低SARS-CoV-2的感染性。因此，本研究的目的是阐明NRP-1在患有AIS的COVID-19患者中的潜在作用。SARS-CoV-2可能通过鼻腔嗅觉上皮中的NRP-1传播至大脑，导致不同的神经功能障碍，因此约45%的COVID-19患者有神经症状。NRP-1具有减轻神经炎症、血脑屏障（BBB）通透性、脑内皮功能障碍（ED）和神经元功能障碍的潜在能力，这些在伴有神经受累（包括AIS）的COVID-19中并不常见。同样，在重症COVID-19患者中，高血清NRP-1水平与ED、氧化应激及肺血栓形成风险相关，提示这是一种克服免疫炎症紊乱的代偿机制。总之，NRP-1在COVID-19和AIS的发病机制中起重要作用，可能是与COVID-19中AIS发生相关的潜在生物标志物。本研究结果不能提供最终结论，因此建议进行计算机模拟、实验、体外、体内、临床前和临床研究，以证实NRP-1在COVID-19中的潜在作用，并阐明NRP-1受体激动剂和拮抗剂在COVID-19中的药理作用。
