Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity.
Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity.
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DOI：
10.3390/antiox10020209
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发表时间：
2021-02-01
期刊：
影响因子：
--
通讯作者：
Kwon HJ
中科院分区：
文献类型：
--
作者：
Cho KH;Kim JR;Lee IC;Kwon HJ
人类高密度脂蛋白(高密度脂蛋白)在抗感染方面显示出广泛的抗病毒活性。尽管许多报告指出血清高密度脂蛋白胆固醇水平较低与新冠肺炎感染和进展的风险较高相关，但高密度脂蛋白体外抗SARS-CoV-2活性尚未见报道。高密度脂蛋白的功能，如抗氧化剂和抗感染，可能会因氧化和糖基化以及促炎特性的改变而受损。本研究通过果糖基化和天然低密度脂蛋白比较了天然高密度脂蛋白和糖化高密度脂蛋白的抗病毒活性。糖化的高密度脂蛋白在72h后呈现典型的多聚体蛋白质图谱，并伴有黄色荧光的增强。与天然高密度脂蛋白相比，糖化高密度脂蛋白显示出较小的颗粒尺寸和模糊的形状，对氧磷酶活性损失高达51%。糖化高密度脂蛋白对乙酰化低密度脂蛋白的吞噬作用是天然高密度脂蛋白的1.3倍。在Vero E6细胞中，天然高密度脂蛋白在60μg/mL(最终浓度约为2.2μM)下显示出比糖化高密度脂蛋白高1.7倍的细胞存活率和3.6倍的细胞病变抑制活性。天然高密度脂蛋白显示，CPE的EC50=52.1±1.1μg/m L(约1.8μM)，CC50=79.4±1.5μg/m L(约2.8μM)。计算出天然高密度脂蛋白的选择指数(SI)为1.52。综上所述，天然高密度脂蛋白具有较强的抗SARS-CoV-2活性，且无细胞毒性，而高密度脂蛋白的糖基化会削弱其抗病毒活性。这些结果可能解释了为什么糖尿病或高血压患者对新冠肺炎感染更敏感，死亡风险更高。
Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the antiviral activity of native HDL with glycated HDL via fructosylation and native low-density lipoproteins (LDL). After 72 h of fructosylation, glycated HDL showed a typical multimerized protein pattern with an elevation of yellowish fluorescence. Glycated HDL showed a smaller particle size with an ambiguous shape and a loss of paraoxonase activity up to 51% compared to native HDL. The phagocytosis of acetylated LDL was accelerated 1.3-fold by glycated HDL than native HDL. Native HDL showed 1.7 times higher cell viability and 3.6 times higher cytopathic effect (CPE) inhibition activity against SARS-CoV-2 than that of glycated HDL under 60 μg/mL (approximately final 2.2 μM) in a Vero E6 cell. Native HDL showed EC50 = 52.1 ± 1.1 μg/mL (approximately final 1.8 μM) for the CPE and CC50 = 79.4 ± 1.5 μg/mL (around 2.8 μM). The selective index (SI) of native HDL was calculated to be 1.52. In conclusion, native HDL shows potent antiviral activity against SARS-CoV-2 without cytotoxicity, while the glycation of HDL impairs its antiviral activity. These results may explain why patients with diabetes mellitus or hypertension are more sensitive to a COVID-19 infection and have a higher risk of mortality.
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