Eugenol, a Component of Holy Basil (Tulsi) and Common Spice Clove, Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses.
Eugenol, a Component of Holy Basil (Tulsi) and Common Spice Clove, Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses.
复制标题
DOI：
10.1007/s11481-021-10028-1
复制
发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Pahan K
中科院分区：
文献类型：
--
作者：
Paidi RK;Jana M;Raha S;McKay M;Sheinin M;Mishra RK;Pahan K
2型严重急性呼吸道综合征冠状病毒（SARS-CoV-2）的刺突S1与宿主细胞上的血管紧张素转换酶2（ACE 2）结合，进入细胞并引发COVID-19。由于ACE 2是一种有利的酶，我们有兴趣找到一种能够结合刺突S1而不是ACE 2的分子，并抑制刺突S1和ACE 2之间的相互作用。圣罗勒（Tulsi）作为不同人类疾病的药物有着悠久的历史。因此，我们筛选了塔尔西叶的不同组分，并发现丁香酚而不是其他主要组分（例如熊果酸、油酸和β-香石竹碱）在基于AlphaScreen的测定中抑制加标S1和ACE 2之间的相互作用。通过计算机模拟分析和热位移分析，我们还观察到丁香酚与尖峰S1相关，但不与ACE 2相关。因此，丁香酚强烈抑制假型SARS-CoV-2进入表达ACE 2的HEK 293细胞，但不抑制水泡性口炎病毒（VSV）。丁香酚还降低SARS-CoV-2峰电位S1诱导的人A549肺细胞中NF-κB的活化以及IL-6、IL-1β和TNFα的表达。此外，在SARS-CoV-2刺突S1中毒小鼠中，丁香酚口服治疗减轻了肺部炎症，降低了发热，改善了心脏功能，并增强了运动活动。因此，丁香酚选择性靶向SARS-CoV-2尖峰S1，而不是ACE 2，可能对COVID-19治疗有益。
Spike S1 of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19. Since ACE2 is a favorable enzyme, we were interested in finding a molecule capable of binding spike S1, but not ACE2, and inhibiting the interaction between spike S1 and ACE2. Holy basil (Tulsi) has a long history as a medicine for different human disorders. Therefore, we screened different components of Tulsi leaf and found that eugenol, but not other major components (e.g. ursolic acid, oleanolic acid and β-caryophylline), inhibited the interaction between spike S1 and ACE2 in an AlphaScreen-based assay. By in silico analysis and thermal shift assay, we also observed that eugenol associated with spike S1, but not ACE2. Accordingly, eugenol strongly suppressed the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus (VSV), into human ACE2-expressing HEK293 cells. Eugenol also reduced SARS-CoV-2 spike S1-induced activation of NF-κB and the expression of IL-6, IL-1β and TNFα in human A549 lung cells. Moreover, oral treatment with eugenol reduced lung inflammation, decreased fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of SARS-CoV-2 spike S1, but not ACE2, by eugenol may be beneficial for COVID-19 treatment.
登录
查看更多内容
美烯醇诱导的癌细胞凋亡的抗增生性和分子机制。
DOI：
10.3390/molecules17066290
发表时间：
2012-05-25
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Jaganathan SK;Supriyanto E
通讯作者：
Supriyanto E
影响因子：
6.2
作者：
Jana, Arundhati;Modi, Khushbu K.;Roy, Avik;Anderson, John A.;van Breemen, Richard B.;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
DOI：
10.1007/s11481-020-09979-8
发表时间：
2021-03
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Paidi RK;Jana M;Mishra RK;Dutta D;Raha S;Pahan K
通讯作者：
Pahan K
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：
--
DOI：
10.1038/s41577-020-00432-8
发表时间：
2020-10-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Pia, Luisanna
通讯作者：
Pia, Luisanna