基于阿巴,肝素或尾酒的S1-ACE2蛋白质复合物的抑制
1Department of Forensic Science, Trent University, Peterborough, Canada.
Analytical biochemistry
|June 29, 2023
概括
对抗SARS-CoV-2 S1-ACE2结合的阿巴和肝素进行了比较. 肝素对某些变种显示出有效性,提供了潜在的成本效益高的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 生物化学 生化学
- 药物发现 药物发现 药物发现
背景情况:
- 严重急性呼吸系统综合征2 (SARS-CoV-2) 结合血管酶转化酶2 (ACE2) 的尖端蛋白 (S1) 对于病毒的进入至关重要.
- 针对S1-ACE2接口是一个有前途的抗病毒治疗策略.
研究的目的:
- 评估阿巴,肝素及其组合对SARS-CoV-2 S1-ACE2复合物的抗病毒疗效.
- 为了比较野生型 (WT),Omicron,Delta和Lambda变种之间的抑制.
主要方法:
- 使用阿巴,肝素和尾酒对抗各种SARS-CoV-2 S1-ACE2复合体进行了抑制试验.
- 确定了解离常数 (KD) 和半最大抑制度 (IC50).
- 用分子建模来理解结合相互作用.
主要成果:
- 阿普塔默-蛋白质复合体对WT S1-ACE2.2.表现出高亲和力 (2-13 nM KD) 和强大的抑制 (17 nM IC50) 对WT S1-ACE2.2.
- 氨酸的抑制作用在S1变体之间有显著的差异,对WT没有抑制,但对突变物有有效性.
- 与单个药物相比,阿普塔默-赫巴林尾酒的疗效有所降低.
结论:
- 氨酸对特定的SARS-CoV-2变种的疗效与阿普坦剂相当.
- 肝素代表了新兴冠状病毒的潜在更具成本效益的中和剂.
- 既能与S1受体结合域 (RBDs) 结合的阿巴和肝素都会干扰ACE2相互作用.
相关概念视频
Anticoagulant Drugs: Low-Molecular-Weight Heparins
763
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
763
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
566
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
566
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
698
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
698
Antihypertensive Drugs: Direct Renin Inhibitors
699
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
699
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
467
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
467
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
1.2K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
1.2K


