Oliveira Katelin X, Suzuki Yuichiro J
bioRxiv. 2024 Dec 13:2024.12.12.628247. doi: 10.1101/2024.12.12.628247.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that caused the Coronavirus Disease 2019 (COVID-19) pandemic, has a spike glycoprotein that is involved in recognizing and fusing to host cell receptors, such as angiotensin-converting enzyme 2 (ACE2), neuropilin-1 (NRP1), and AXL tyrosine-protein kinase. Since the major spike protein receptor is ACE2, an enzyme that regulates angiotensin II (1-8), this study tested the hypothesis that angiotensin II (1-8) influences the binding of the spike protein to its receptors. While angiotensin II (1-8) did not influence spike-ACE2 binding, we found that it significantly enhances spike-AXL binding. Our experiments showed that longer lengths of angiotensin, such as angiotensin I (1-10), did not significantly affect spike-AXL binding. In contrast, shorter lengths of angiotensin peptides, in particular, angiotensin IV (3-8), strongly increased spike-AXL binding. Angiotensin IV (3-8) also enhanced spike protein binding to ACE2 and NRP1. The discovery of the enhancing effects of angiotensin peptides on spike-host cell receptor binding may suggest that these peptides could be pharmacological targets to treat COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), which is also known as long COVID.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是导致2019年冠状病毒病（COVID-19）大流行的病毒，它有一种刺突糖蛋白，参与识别并与宿主细胞受体融合，如血管紧张素转换酶2（ACE2）、神经纤毛蛋白-1（NRP1）和AXL酪氨酸蛋白激酶。由于主要的刺突蛋白受体是ACE2，一种调节血管紧张素II（1-8）的酶，本研究检验了血管紧张素II（1-8）影响刺突蛋白与其受体结合的假说。虽然血管紧张素II（1-8）不影响刺突蛋白与ACE2的结合，但我们发现它能显著增强刺突蛋白与AXL的结合。我们的实验表明，较长长度的血管紧张素，如血管紧张素I（1-10），对刺突蛋白与AXL的结合没有显著影响。相反，较短长度的血管紧张素肽，特别是血管紧张素IV（3-8），能强烈增加刺突蛋白与AXL的结合。血管紧张素IV（3-8）还增强了刺突蛋白与ACE2和NRP1的结合。血管紧张素肽对刺突蛋白与宿主细胞受体结合具有增强作用这一发现可能表明，这些肽可能成为治疗COVID-19和SARS-CoV-2急性后遗症（PASC，也称为长期新冠）的药理学靶点。
