3CLpro, 3C-like protease

  • 文章类型: Journal Article
    未经批准:2019年12月,一种新型冠状病毒,SARS-CoV-2在全球范围内引起一系列急性非典型呼吸道疾病。然而,仍然缺乏疗效明确的药物,疫苗的临床试验研究尚未完全完成。
    UASSIGNED:LH胶囊是批准的中药成药,广泛用于治疗由感冒和流感引起的呼吸道传染病。2020年4月12日,根据通过多中心证明的安全性和有效性,中国食品药品监督管理局(CFDA)正式将LH胶囊和颗粒重新用于轻度COVID-19患者,随机化,对照临床试验。我们希望通过现代药学方法对其进行全面回顾,并试图解释其可能的机制。
    未经授权:使用连花清温黄体胶囊的全称,连花清温和SARS-COV-2、COVID-19作为搜索词的关键词,在各种数据库(如WebofScience和PubMed)中系统地搜索现有的相关论文。并在ClinicalTrials.gov和中国临床试验注册中心完成了临床数据的收集。最后但并非最不重要的,我们通过文献和Selleck整理了LH胶囊的抗炎和抗病毒机制。
    UNASSIGNED:这篇综述系统地梳理了LH胶囊中的活性成分。此外,详细讨论了LH胶囊对SARS-CoV-2,IAV和IBV的相关药理和临床试验。此外,本综述首次概述了LH胶囊中特定物质参与SARS-COV-2感染抗性和抑制IL-6引起的细胞因子风暴综合征(CSS)的潜在分子机制。
    UNASSIGNED:本综述总结了支持使用LH胶囊作为预防和治疗COVID-19的潜在候选药物的现有报告和证据。然而,中医通过多靶点、多途径发挥作用,LH胶囊也不例外。因此,相关机制有待进一步完善和实验验证。
    UNASSIGNED: In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished.
    UNASSIGNED: LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism.
    UNASSIGNED: Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck.
    UNASSIGNED: This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6.
    UNASSIGNED: This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified.
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  • 文章类型: Journal Article
    迫切需要更安全、更有效的药物来对抗导致COVID-19大流行的高致病性SARS-CoV-2感染。鉴定治疗和预防SARS-CoV-2感染的有效抑制剂是主要的焦点。令人鼓舞的是,使用治疗相关药物靶标的X射线晶体结构(PLpro,Mpro,RdRp,和S糖蛋白)通过直接可视化相互作用为抗SARS-CoV-2药物发现和引导优化提供了有价值的方向。还提出了主要基于MMPBSA计算的计算分析用于评估涉及配体和受体的生物分子结构的结合稳定性。在这项研究中,我们专注于与新鉴定的小分子抑制剂(天然产物,FDA批准的药物,候选药物,及其类似物),并借助计算分析来支持抗SARS-CoV-2药物的精确设计和筛选。
    Safer and more-effective drugs are urgently needed to counter infections with the highly pathogenic SARS-CoV-2, cause of the COVID-19 pandemic. Identification of efficient inhibitors to treat and prevent SARS-CoV-2 infection is a predominant focus. Encouragingly, using X-ray crystal structures of therapeutically relevant drug targets (PLpro, Mpro, RdRp, and S glycoprotein) offers a valuable direction for anti-SARS-CoV-2 drug discovery and lead optimization through direct visualization of interactions. Computational analyses based primarily on MMPBSA calculations have also been proposed for assessing the binding stability of biomolecular structures involving the ligand and receptor. In this study, we focused on state-of-the-art X-ray co-crystal structures of the abovementioned targets complexed with newly identified small-molecule inhibitors (natural products, FDA-approved drugs, candidate drugs, and their analogues) with the assistance of computational analyses to support the precision design and screening of anti-SARS-CoV-2 drugs.
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  • 文章类型: Journal Article
    一种严重的肺炎,被世界卫生组织命名为2019年冠状病毒病(COVID-19),在中国爆发并迅速发展成为全球大流行,全球报告了数百万例病例和数十万例死亡病例。新型冠状病毒,被指定为严重急性呼吸道综合症冠状病毒2(SARS-CoV-2),被确定为COVID-19的病原体。根据以往SARS-CoV和MERS-CoV爆发和研究积累的经验,一系列研究迅速进行,在理解SARS-CoV-2的系统发育和基因组组织以及其感染和复制的分子机制方面取得了重大进展。在本次审查中,我们总结了在阐明SARS-CoV-2关键蛋白的结构和功能方面的重要进展,尤其是主要的蛋白酶,RNA依赖性RNA聚合酶,刺突糖蛋白,和核衣壳蛋白。有关其相关抑制剂和药物的研究结果也得到了强调。
    A severe form of pneumonia, named coronavirus disease 2019 (COVID-19) by the World Health Organization, broke out in China and rapidly developed into a global pandemic, with millions of cases and hundreds of thousands of deaths reported globally. The novel coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of COVID-19. On the basis of experience accumulated following previous SARS-CoV and MERS-CoV outbreaks and research, a series of studies have been conducted rapidly, and major progress has been achieved with regard to the understanding of the phylogeny and genomic organization of SARS-CoV-2 in addition its molecular mechanisms of infection and replication. In the present review, we summarized crucial developments in the elucidation of the structure and function of key SARS-CoV-2 proteins, especially the main protease, RNA-dependent RNA polymerase, spike glycoprotein, and nucleocapsid protein. Results of studies on their associated inhibitors and drugs have also been highlighted.
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  • 文章类型: Journal Article
    由SARS-CoV-19引起的Covid-19疾病的爆发,以及缺乏针对性的药物和疫苗,迫使科学界寻找新的抗病毒制剂。在这次审查中,我们描述了目前关于含有抑制新冠肺炎的多酚的植物提取物的知识。许多植物来源的天然化合物(多酚)可能为研究植物提取物在冠状病毒治疗和预防中的应用提供了起点。抗病毒多酚药物可以抑制冠状病毒酶,这对病毒复制和感染至关重要。这组天然物质(桦木酸,靛蓝,aloeeemodine,木犀草素,和五甲基三萜类,槲皮素或没食子酸酯)是设计抑制病毒蛋白酶的抗病毒疗法的潜在关键。生物活性物质的已知药效团结构可用于制备新的抗新冠肺炎制剂。使用含有植物化学物质的制剂的好处是它们对患者的高安全性并且没有副作用。
    The outbreak of Covid-19 disease caused by SARS-CoV-19, along with the lack of targeted medicaments and vaccines, forced the scientific world to search for new antiviral formulations. In this review, we describe the current knowledge about plant extracts containing polyphenols that inhibit Covid-19. Many plant-derived natural compounds (polyphenols) might provide a starting point for the research on the use of plant extracts in coronavirus treatment and prevention. Antivirus polyphenolic drugs can inhibit coronavirus enzymes, which are essential for virus replication and infection. This group of natural substances (betulinic acid, indigo, aloeemodine, luteolin, and quinomethyl triterpenoids, quercitin or gallates) is a potential key to designing antiviral therapies for inhibiting viral proteases. The known pharmacophore structures of bioactive substances can be useful in the elaboration of new anti-Covid-19 formulations. The benefit of using preparations containing phytochemicals is their high safety for patients and no side effects.
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  • 文章类型: Journal Article
    席夫碱是广泛使用的通用有机化合物,其通过不同的氨基化合物与被称为亚胺的醛或酮的缩合反应合成。席夫碱配体被认为是特权配体,因为它们通过缩合简单地合成。它们在医学上显示出广泛的应用,药房,配位化学,生物活动,工业,食品包装,染料,和聚合物,也用作O2检测器。半脲是衍生自氨基脲与合适的醛和酮缩合的亚胺衍生物。含亚胺配体的过渡金属配合物如铜,锌,和镉已被证明是合成金属或金属硫属化物纳米颗粒的优异前体。近年来,研究人员对希夫碱基引起了极大的关注,氨基脲,氨基硫脲,和它们的金属配合物,由于在药理学中的许多应用,如抗病毒,抗真菌药,抗菌,抗疟药,抗结核药,抗癌,抗艾滋病毒,在有机化合物氧化中的催化应用,和纳米技术。在这次审查中,我们总结了合成,结构,生物,席夫碱及其金属配合物的催化应用。
    Schiff bases are versatile organic compounds which are widely used and synthesized by condensation reaction of different amino compound with aldehydes or ketones known as imine. Schiff base ligands are considered as privileged ligands as they are simply synthesized by condensation. They show broad range of application in medicine, pharmacy, coordination chemistry, biological activities, industries, food packages, dyes, and polymer and also used as an O2 detector. Semicarbazone is an imine derivative which is derived from condensation of semicarbazide and suitable aldehyde and ketone. Imine ligand-containing transition metal complexes such as copper, zinc, and cadmium have shown to be excellent precursors for synthesis of metal or metal chalcogenide nanoparticles. In recent years, the researchers have attracted enormous attention toward Schiff bases, semicarbazones, thiosemicarbazones, and their metal complexes owing to numerous applications in pharmacology such as antiviral, antifungal, antimicrobial, antimalarial, antituberculosis, anticancer, anti-HIV, catalytic application in oxidation of organic compounds, and nanotechnology. In this review, we summarize the synthesis, structural, biological, and catalytic application of Schiff bases as well as their metal complexes.
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