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首页> 外文期刊>Biochemical Pharmacology >The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations
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The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

机译:无机聚合物,多相磷酸盐,在生理浓度下阻断SARS-COV-2穗蛋白与ACE2受体的结合

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摘要

Inorganic polyphosphate (polyP) is a morphogenetically active and metabolic energy-delivering physiological polymer that is released from blood platelets. Here, we show that polyP efficiently inhibits the binding of the envelope spike (S)-protein of the coronavirus SARS-CoV-2, the causative agent of COVID-19, to its host cell receptor ACE2 (angiotensin-converting enzyme 2). To stabilize polyP against the polyP-degrading alkaline phosphatase, the soluble polymer was encapsulated in silica/polyP nanoparticles. Applying a binding assay, soluble Na-polyP (sizes of 40 Pi and of 3 Pi units) as well as silica-nanoparticle-associated polyP significantly inhibit the interaction of the S-protein with ACE2 at a concentration of 1 mu g/mL, close to the level present in blood. This inhibition is attributed to an interaction of polyP with a basic amino acid stretch on the surface of the receptor binding domain of S-protein. PolyP retains its activity in a flushing solution, opening a new strategy for the prevention and treatment of SARS-CoV-2 infection in the oropharyngeal cavity. The data suggest that supplementation of polyP might contribute to a strengthening of the human innate immunity system in compromised, thrombocytopenic COVID-19 patients.
机译:无机多磷酸盐(息肉)是从血小板血小板中释放的形态发生活性和代谢能量输送的生理聚合物。这里,我们表明息肉有效地抑制冠状病毒SARS-COV-2,Covid-19的致病剂的包络穗 - COV-2的结合到其宿主细胞受体ACE2(血管紧张素转换酶2)。为了将息肉稳定在息肉降解碱性磷酸酶上,将可溶性聚合物包封在二氧化硅/息肉纳米粒子中。施加结合测定,可溶性Na-π-息肉(尺寸为40 pi和3 pi单元)以及二氧化硅纳米颗粒相关息肉,显着抑制S-蛋白质与αce2的浓度为1μg/ ml的相互作用,接近血液中存在的水平。该抑制归因于息肉与S蛋白的受体结合结构域的表面表面上的碱性氨基酸的相互作用。息肉在冲洗解决方案中保持其活性,开启了在口咽腔内预防和治疗SARS-COV-2感染的新策略。数据表明,息肉的补充可能有助于加强受损的血小板减少患者患者的人体先天免疫系统。

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