The Important Herbal Pair for the Treatment of COVID-19 and Its Possible Mechanisms

Abstract

Background: Corona Virus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicines(TCM) are indeed effective in treating COVID-19. However, it is a hard work to find the most effective combination laws among numerous herbs as well as its potential mechanisms. The purpose of this article is to explore the combination laws of traditional Chinses medicine(TCM) prescriptions and pick out the most important herbal pair for treating COVID-19 and analyze the active components and potential mechanisms. Methods: We first systematically sorted out the TCM prescriptions recommended by leading experts for treating COVID-19 and the specific herbs they contained in different stages of disease. Next, the association rule approach was employed to examine the distribution and combination laws among these TCM prescription, and then picked out the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach. Result: We obtained 32 association rules for herb combinations in the process of TCM treatment for COVID-19. It was found that the combination of Amygdalus Communis Vas(ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value as well as high support degree, which can be used in almost all stages of COVID-19, so ACV and ESS (AE) was selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which may be relate to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 are quercetin, kaempferol, luteolin and the potential important targets are Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA) and so on. The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The significant pathways mainly involved in tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), nucleotide-binding oligomerization domain (NOD)-like receptor(NLRs). Conclusion: Amygdalus Communis Vas and Ephedra sinica Stapf was the most important herbal pair in the treatment of COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin and the important targets were IL-6，MAPK1, MAPK8, IL-1β, RELA and so on. AE may have therapeutic effects against COVID-19 by affecting the pathological processes such as inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, multiple targets and multiple pathways.

Network Pharmacology-Based Study of the Underlying Mechanisms of Huangqi Sijunzi Decoction for Alzheimer’s Disease

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A Vibrational Signal Fault Diagnosis Rule Extraction Method Based on DST‐ACI Discriminant Criterion

“…en, the obtained knowledge can be put into industrial or commercial applications [10][11][12]. erefore, the two technologies have been widely used in many fields such as disease diagnosis, traffic management, weather forecasting, software testing, and commercial marketing [13][14][15][16][17][18][19].…”

Recent advances in 3CL<sup>pro</sup> inhibitors from Chinese herbs

“…得到证实 [32,39,40] 。Cys145/148 得益于形成的氧负离子洞和稳定的去质子化的巯基，可以特异性地稳定 并结合进攻谷氨酰胺主链的羰基碳原子 [15] 。His41 通过接受 Cys145/148 的质子而被质子化，形成具有 催化活性的电正性咪唑基团，可以质子化催化底物半缩酮的氧原子，当催化反应完成后，去质子化的 组氨酸可以通过一个稳定的水分子来接受 Asp187 传递的电子受 Cys145/148 的质子而被质子化， 形成 具有催化活性的电正性咪唑基团，可以质子化催化底物半缩酮的氧原子，当下一轮催化反应激活，该 水分子通过氢键网络结合 His164/Gln167，His41 和 Asp187/190 在活性位点内部稳定存在 [41] 。 表 1 SARS-CoV-2 3CL pro 、SARS-CoV 3CL pro 和 MERS-CoV 3CL pro 的分子特征 [29,35,36,[41][42][43] 。 [44][45][46] 。这也提示着中 草药中的某些活性成分能通过靶向冠状病毒的关键靶标，从而阻碍病毒的复制和增殖过程。为了揭示 中草药的抗病毒机制并为新型的抗病毒药物的开发提供科学依据，越来越多的研究表明，许多中药提 取物及其化学成分显示出对 3CL pro 较好的抑制作用。表 2 总结了多种中草药提取物对 3CL pro 的抑制 作用，特别是黄芩、藤茶、银杏叶、诃子、茶等提取物对 3CL pro 具有显著的抑制作用 [47][48][49][50][51][52][53][54][55][56][57][58][59] 。尽管…”