Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2.
Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2.
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DOI：
10.3390/ijms232012565
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发表时间：
2022-10-19
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV的功能性受体血管紧张素转换酶2（ACE 2）现在似乎可能介导2019-nCoV进入人类细胞。然而，已经发现了抑制剂如PAP-1和香柠檬素;它们都可以优先结合ACE 2，阻止RBD Spike S蛋白与ACE 2结合，并减少RBD Spike S蛋白的结合位点。此外，我们研究了PAP-1和香柠檬素与ACE 2的结合能，通过分子对接与生物层干涉法（BLI），发现PAP-1和香柠檬素基团之间的相对较高的结合亲和力（KD = 48.5 nM，53.1 nM）。此外，纳摩尔级分对AT-II细胞的生长没有影响，但150 μM PAP-1和75 μM香柠檬素在体外分别抑制了AT-II细胞的增殖75%和68%。同时，它们显著降低ACE 2 mRNA和蛋白水平，分别为67%、58%和55%、41%。这些结果表明，在当前大流行期间，可以进一步开发结合ACE 2蛋白的补骨脂素化合物PAP-1和香柠檬素，以对抗COVID-19感染。但应注意对人肺泡II型上皮细胞的损伤。
Angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. However, inhibitors such as PAP-1 and bergamottin have been discovered; both of them can preferentially bind to ACE2, prevent RBD Spike S protein from binding to ACE2, and reduce the binding sites for RBD Spike S protein. In addition, we investigated the binding energy of PAP-1 and bergamottin with ACE2 through molecular docking with bio-layer interferometry (BLI) and found relatively high binding affinity (KD = 48.5 nM, 53.1 nM) between the PAP-1 and bergamottin groups. In addition, the nanomolar fraction had no effect on growth of the AT-II cell, but 150 µM PAP-1 and 75 µM bergamottin inhibited the proliferation of AT-II cells in vitro by 75% and 68%, respectively. Meanwhile, they significantly reduced ACE2 mRNA and proteins by 67%, 58% and 55%, 41%, respectively. These results indicate that psoralen compounds PAP-1 and bergamottin binding to ACE2 protein could be further developed in the fight against COVID-19 infection during the current pandemic. However, attention should be paid to the damage to human alveolar type II epithelial cells.
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