Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry.
Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry.
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DOI：
10.1038/s41598-021-84850-1
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发表时间：
2021-03-04
影响因子：
4.6
通讯作者：
Rath M
中科院分区：
文献类型：
--
作者：
Goc A;Niedzwiecki A;Rath M
2019年底新出现的SARS-CoV-2菌株已被确定为COVID-19和WHO于2020年初宣布的大流行的病因。虽然脂质已被证明具有抗病毒功效，但目前对具有抗SARS-CoV-2结合和进入性质的脂质化合物知之甚少。为了解决这个问题，我们筛选，总体上，17多不饱和脂肪酸，单不饱和脂肪酸和饱和脂肪酸，作为脂溶性维生素的威尔斯井。在利用RBD-SARS-CoV-2序列进行基于靶点的配体筛选时，我们观察到多不饱和脂肪酸最有效地干扰与SARS-CoV-2受体hACE 2的结合。使用刺突蛋白假病毒，我们还发现亚麻酸和二十碳五烯酸显著阻断SARS-CoV-2的进入。此外，二十碳五烯酸在降低TMPRSS 2和组织蛋白酶L蛋白酶活性方面显示出比亚麻酸更高的功效，但这两种脂肪酸都不影响它们在蛋白质水平上的表达。此外，在用这两种脂肪酸处理后，既没有观察到hACE 2活性的降低，也没有观察到与hACE 2受体的结合。虽然进一步的体内实验是必要的，以验证目前的研究结果，我们的研究提供了一个新的见解脂质作为抗病毒化合物对SARS-CoV-2菌株的作用。
The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.
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影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
4.9
作者：
KOHN, A;GITELMAN, J;INBAR, M
通讯作者：
INBAR, M
DOI：
10.1038/nrmicro2090
发表时间：
2009-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Matsuyama, Shutoku;Nagata, Noriyo;Taguchi, Fumihiro
通讯作者：
Taguchi, Fumihiro