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从传统印度医学角度理解免疫系统对抗 COVID-19 的激活机制:网络药理学方法。

Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach.

机构信息

Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, India.

Siddha Central Research Institute (CCRS), Chennai, India.

出版信息

Adv Protein Chem Struct Biol. 2022;129:275-379. doi: 10.1016/bs.apcsb.2021.11.007. Epub 2022 Jan 29.

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5″-(2⁗-Hydroxybenzyl) uvarinol, antofine, (S)-1'-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10α-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.

摘要

严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)传播迅速,在全球范围内引发警报。尽管目前已有疫苗,但 SARS-CoV-2 的不断进化和突变威胁到现有疫苗的作用。这些药物仍在临床试验中,某些药物在大流行期间被批准“紧急使用”或作为“标签外”药物。这些药物虽然有效,但也有副作用,有些副作用甚至可能致命。由于补充和替代医学采用整体方法,因此需求量很大。自古以来,天然产物就被用作药物来治疗医学领域的各种疾病,并且仍然广泛应用。药用植物含有许多作为有效药物设计关键的活性化合物。卡巴苏拉库丁和尼拉夫姆库丁是两种最广泛批准用于治疗 COVID-19 的配方。然而,这些配方的机制尚不清楚。本研究采用网络药理学方法,了解卡巴苏拉库丁、尼拉夫姆库丁和 JACOM 治疗 COVID-19 的免疫增强机制。从文献中获取卡巴苏拉库丁、尼拉夫姆库丁和 JACOM 中的植物和植物化学化合物。使用瑞士靶标预测算法预测这些植物化学化合物的靶标。确定了 COVID-19 感染和药物靶标共同的基因。构建基因-基因相互作用网络,了解这些共同基因之间的相互作用,并进行富集分析,确定涉及的生物过程、分子功能、细胞功能、途径等。最后,进行虚拟筛选和分子对接研究,以确定最有潜力的靶标和治疗 COVID-19 的重要植物化学化合物。本研究确定了 ACE、组织蛋白酶 L、组织蛋白酶 B、组织蛋白酶 K、二肽基肽酶 4、表皮生长因子受体、组蛋白去乙酰化酶 2、白细胞介素 6、RIPK1 和血管内皮生长因子 A 等潜在靶标。同样,齐墩果酸、5″-(2⁗-羟基苄基)乌伐醇、安托芬、(S)-1'-甲基辛基咖啡酸酯、(Z)-3-苯基-2-丙烯醛、7-酮-10α-葫芦二烯醇和 PLX-4720 也被共同确定为 COVID-19 的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7205/8798878/7da26c670321/f09-01-9780323992275_lrg.jpg

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