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From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from Genus Artemisia. 从传统用途到现代证据:蒿属抗疟药物的药物化学》。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575320559240820113540
Abdur Rauf, Ahmed Olatunde, Nabia Hafeez, Hassan A Hemeg, Abdullah S M Aljohani, Waleed Al Abdulmonem, Giovanni Ribaudo

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and nature-inspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

虽然植物在传统医学中的应用可以追溯到公元前 1500 年,但现代医学的进步促进了创新治疗技术的发展。另一方面,在抗感染药物领域,疗效不佳和抗药性的出现也促使人们寻找新的药物。青蒿属是多年生植物中最多样化的植物之一,其种类、特性和化学成分多种多样。该属植物因其治疗价值而闻名,特别是在青蒿素抗疟药物的起源中扮演着重要角色。在这篇综述中,我们旨在提供与青蒿属有关的天然和受自然启发的化合物的最新演化概况,这些化合物已在体外和体内被证实具有抗疟特性。报告将概述青蒿素及其衍生物的化学成分和民族药理学方面的描述,以及体外和体内证据的最新报告,这些证据使得青蒿素及其衍生物从传统化学转化为现代药物化学。此外,还将讨论青蒿素及其衍生物的生物和结构特性,并关注仍有待完成的挑战性任务,如确定最佳组合策略、给药途径和对作用机制的全面评估。
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引用次数: 0
Synthetic Methods of Quinoxaline Derivatives and their Potential Anti-inflammatory Properties. 喹喔啉衍生物的合成方法及其潜在的抗炎特性。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575307480240610055622
Anjali, Payal Kamboj, Mohammad Amir

Quinoxaline molecule has gathered great attention in medicinal chemistry due to its vide spectrum of biological activities and has emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises a bicyclic ring of benzopyrazine and displays a range of pharmacological properties, including antibacterial, antifungal, antiviral, anticancer, and antiinflammatory. This study aims to summarize the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure-activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better antiinflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on the expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and p38α Mitogen Activated Protein Kinase (p38α MAPK). Activators of nuclear factor erythroid 2-related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this study may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profiles.

喹喔啉分子因其广泛的生物活性而在药物化学领域备受关注,并成为药物发现和开发中的多功能药层。它的结构由苯并吡嗪的双环组成,具有抗菌、抗真菌、抗病毒、抗癌和抗炎等一系列药理特性。本综述总结了合成喹喔啉类化合物的不同策略及其通过不同机制发挥作用的抗炎特性。此外,还讨论了结构活性关系,以确定结构修饰对抗炎潜力的影响。这些分析揭示了最佳活性所需的关键结构特征,从而推动了具有更好抗炎活性的新喹喔啉类似物的设计和合成。喹喔啉类化合物的抗炎特性归因于它们对几种炎症调节因子表达的抑制作用,如环氧化酶、细胞因子、活化 B 细胞的核因子卡帕-轻链-增强因子(NFB)和 p38 丝裂原活化蛋白激酶(p38 MAPK)。此外,还讨论了核因子红细胞 2 相关因子 2(NRF2)的激活剂以及对阿片受体的激动作用。因此,本综述可为今后设计和开发通过不同分子靶点发挥作用的新型喹喔啉衍生物提供模板,使其成为具有更好疗效和安全性的潜在抗炎药物。.
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引用次数: 0
Exploring Genetic Silencing: RNAi and CRISPR-Cas Potential against Drug Resistance in Malaria. 探索基因沉默:RNAi 和 CRISPR-Cas 对抗疟疾抗药性的潜力。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575306957240610102626
Carlos Gaona-Lopez, Gildardo Rivera

Malaria has been one of the most lethal infectious diseases throughout history, claiming a high number of human lives. The genomic plasticity of Plasmodium falciparum, the causative agent of the most severe and deadly form of malaria, gives the parasite a constant resistance to drugs developed for its control. Despite efforts to control and even eradicate the disease, these have largely been unsuccessful due to the parasite's continuous adaptations. This study aims to examine the key genes involved in parasite resistance and propose a shift in the combat strategy. Gene silencing techniques offer promise in combating malaria, yet further research is needed to harness their potential for disease control fully. Although there is still a long way to go for the implementation of gene silencing-based therapeutic strategies, this review addresses examples of the use of such techniques in various human diseases and how they could be extrapolated for malaria treatment.

疟疾是有史以来最致命的传染病之一,夺去了大量人的生命。恶性疟原虫是最严重和最致命的疟疾的病原体,其基因组的可塑性使寄生虫对为控制疟疾而开发的药物具有持续的抗药性。尽管人们一直在努力控制甚至根除这种疾病,但由于寄生虫的不断适应性,这些努力基本上都没有成功。这项研究旨在研究寄生虫抗药性所涉及的关键基因,并提出应对策略的转变。基因沉默技术为抗击疟疾带来了希望,但要充分发挥其控制疾病的潜力,还需要进一步的研究。尽管实施基于基因沉默的治疗策略还有很长的路要走,但这篇综述讨论了在各种人类疾病中使用此类技术的实例,以及如何将它们推广到疟疾治疗中。
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引用次数: 0
Nimbolide: A Potential Phytochemical Agent in Multimodal Pancreatic Cancer Therapies. Nimbolide:胰腺癌多模式疗法中的潜在植物化学制剂
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575293138240527061556
Mukesh Jogi, Hitakshi Asnani, Sohini Singh, Pramod Kumar

A significant contributor to cancer-related death, pancreatic cancer (PC) has a terrible prognosis in general that has not altered over many years. Currently, it is extremely difficult to prevent disease or discover it early enough to initiate treatment. PC is a challenging malignancy to treat, and several major impediments significantly impact the effectiveness of its treatment. These obstacles primarily include chemoresistance, drug toxicity, and limited drug bioavailability. Phytochemicals can be used as an alternative to chemotherapeutic drugs, or they can augment the anticancer properties of the chemotherapeutic agents. Nimbolide (NL) is a prominent limonoid compound found in Azadirachta indica, and has garnered substantial attention as a phytochemical with anticancer potential. It has powerful antiproliferative effects on a variety of cancer cell lines and is effective as a chemotherapeutic in preclinical studies. The primary modes of action of NL include suppression of metastasis and angiogenesis, activation of apoptosis, anti-proliferation, and control of enzymes that metabolize carcinogens. Despite numerous pharmacodynamic (PD) investigations, NL is still in the early stages of the drug development process because no comprehensive pharmacokinetic studies or long-term toxicity studies. Preclinical and toxicological assessments should be conducted to establish an appropriate dosage range, ensuring the safety of NL for its application in initial human clinical trials. This review endeavors to provide a comprehensive summary of the current developmental stage of NL along with nanoparticles as a principal candidate for therapeutic purposes in PC.

胰腺癌(PC)是导致癌症相关死亡的一个重要因素,其预后很差,多年来一直没有改变。目前,预防胰腺癌或及早发现胰腺癌以启动治疗极其困难。PC 的主要挑战是获得性化疗耐药性,这使其非常难以控制。PC 是一种极具挑战性的恶性肿瘤,几大障碍严重影响了其治疗效果。这些障碍主要包括化疗耐药性、药物毒性和有限的药物生物利用度。植物化学物质可以作为化疗药物的替代品,也可以增强化疗药物的抗癌特性。Nimbolide (NL) 是一种在 Azadirachta indica 中发现的著名柠檬类化合物,作为一种具有抗癌潜力的植物化学物质,它已经引起了广泛关注。它对多种癌细胞系具有强大的抗增殖作用,在临床前研究中可作为一种有效的化疗药物。NL 的主要作用模式包括抑制转移和血管生成、激活细胞凋亡、抗增殖以及控制代谢致癌物质的酶。尽管进行了大量药效学(PD)研究,但由于没有全面的药代动力学(PK)研究或长期毒性研究,NL 仍处于药物开发过程的早期阶段。应进行临床前 PK 和毒理学评估,以确定适当的剂量范围,确保 NL 在初步人体临床试验中应用的安全性。本综述旨在全面总结 NL 目前的发展阶段,以及作为 PC 治疗目的主要候选药物的纳米粒子。
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引用次数: 0
Pharmaceutical Studies on Piperazine-based Compounds Targeting Serotonin Receptors and Serotonin Reuptake Transporters. 针对羟色胺受体和羟色胺再摄取转运体的哌嗪类化合物的药物研究。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575319878240612070850
Cem Yamali, Merve Nenni, Mehtap Tugrak Sakarya, Hasan Alper Kaplan

Depression is a debilitating mental illness that has a significant impact on an individual's psychological, social, and physical life. Multiple factors, such as genetic factors and abnormalities in neurotransmitter levels, contribute to the development of depression. Monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotoninnoradrenaline reuptake inhibitors, and atypical and new-generation antidepressants are well-known drug classes. SSRIs are the commonly prescribed antidepressant medications in the clinic. Genetic variations impacting serotonergic activity in people can influence susceptibility to diseases and response to antidepressant therapy. Gene polymorphisms related to 5-hydroxytryptamine (5-HT) signaling and subtypes of 5-HT receptors may play a role in the development of depression and the response to antidepressants. SSRIs binding to 5-HT reuptake transporters help relieve depression symptoms. Research has been conducted to identify a biomarker for detecting depressive disorders to identify new treatment targets and maybe offer novel therapy approaches. The pharmacological potentials of the piperazine-based compounds led researchers to design new piperazine derivatives and to examine their pharmacological activities. Structure-activity relationships indicated that the first aspect is the flexibility in the molecules, where a linker of typically a 2-4 carbon chain joins two aromatic sides, one of which is attached to a piperazine/phenylpiperazine/benzyl piperazine moiety. Newly investigated compounds having a piperazine core show a superior antidepressant effect compared to SSRIs in vitro/in vivo.

抑郁症是一种使人衰弱的精神疾病,对个人的心理、社交和生理生活都有重大影响。遗传因素和神经递质水平异常等多种因素都会导致抑郁症的发生。单胺氧化酶抑制剂、三环类抗抑郁药、血清素再摄取抑制剂(SSRIs)、血清素-去甲肾上腺素再摄取抑制剂以及非典型和新一代抗抑郁药是众所周知的药物类别。SSRIs 是临床上常用的抗抑郁药物。影响人体内血清素能活性的基因变异可影响对疾病的易感性和对抗抑郁治疗的反应。与5-羟色胺(5-HT)信号传导和5-HT受体亚型有关的基因多态性可能在抑郁症的发病和对抗抑郁药的反应中发挥作用。与 5-HT 再摄取转运体结合的 SSRIs 有助于缓解抑郁症状。研究人员一直在寻找一种检测抑郁症的生物标志物,以确定新的治疗目标,并提供新的治疗方法。哌嗪类化合物的药理潜力促使研究人员设计出新的哌嗪衍生物,并研究它们的药理活性。结构-活性关系表明,首先是分子的灵活性,通常由 2-4 个碳链的连接体连接两个芳香侧,其中一个芳香侧与哌嗪/苯基哌嗪/苄基哌嗪分子相连。与 SSRIs 相比,新研究的以哌嗪为核心的化合物在体外/体内显示出更优越的抗抑郁效果。
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引用次数: 0
A Review on Therapeutic Strategies against Parkinson's Disease: Current Trends and Future Perspectives. 帕金森病治疗策略综述:当前趋势与未来展望。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575303788240606054620
Georgios Papagiouvannis, Panagiotis Theodosis-Nobelos, Eleni A Rekka

Parkinson's Disease (PD) is the most common neurodegenerative disorder after Alzheimer's Disease and is clinically expressed by movement disorders, such as tremor, bradykinesia, and rigidity. It occurs mainly in the extrapyramidal system of the brain and is characterized by dopaminergic neuron degeneration. L-DOPA, dopaminergic agonists, anticholinergic drugs, and MAO-B inhibitors are currently used as therapeutic agents against PD, however, they have only symptomatic efficacy, mainly due to the complex pathophysiology of the disease. This review summarizes the main aspects of PD pathology, as well as, discusses the most important biochemical dysfunctions during PD, and presents novel multi-targeting compounds, which have been tested for their activity against various targets related to PD. This review selects various research articles from main databases concerning multi-targeting compounds against PD. Molecules targeting more than one biochemical pathway involved in PD, expected to be more effective than the current treatment options, are discussed. A great number of research groups have designed novel compounds following the multi-targeting drug approach. They include structures combining antioxidant, antiinflammatory, and metal-chelating properties. These compounds could be proven useful for effective multi-targeted PD treatment. Multi-targeting drugs could be a useful tool for the design of effective antiparkinson agents. Their efficacy towards various targets implicated in PD could be the key to the radical treatment of this neurodegenerative disorder.

帕金森病(PD)是继阿尔茨海默病之后最常见的神经退行性疾病,临床表现为运动障碍,如震颤、运动迟缓和僵直。它主要发生在大脑锥体外系,以多巴胺能神经元变性为特征。目前,左旋多巴酸、多巴胺能激动剂、抗胆碱能药物和 MAO-B 抑制剂被用作治疗帕金森氏症的药物,但它们仅具有对症疗效,这主要是由于该疾病的病理生理学十分复杂。这篇综述总结了帕金森病病理的主要方面,讨论了帕金森病最重要的生化功能障碍,并介绍了新型多靶点化合物,这些化合物已针对与帕金森病相关的各种靶点进行了活性测试。本综述从主要数据库中选取了有关针对帕金森病的多靶点化合物的各种研究文章。文章讨论了针对与帕金森病有关的一个以上生化途径的分子,这些分子有望比目前的治疗方案更有效。许多研究小组采用多靶点药物方法设计了新型化合物。其中包括结合了抗氧化、抗炎和金属螯合特性的结构。事实证明,这些化合物可用于有效的多靶点帕金森病治疗。多靶点药物是设计有效抗帕金森药物的有用工具。它们对与帕金森病有关的各种靶点的疗效可能是彻底治疗这种神经退行性疾病的关键。
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引用次数: 0
Recent Progress of Glutathione Peroxidase 4 Inhibitors in Cancer Therapy. 谷胱甘肽过氧化物酶 4 抑制剂在癌症治疗中的最新进展。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575308546240607073310
Shangde Liu, Jian Wang

Ferroptosis is a novel type of programmed cell death that relies on the build-up of intracellular iron and leads to an increase in toxic lipid peroxides. Glutathione Peroxidase 4 (GPX4) is a crucial regulator of ferroptosis that uses glutathione as a cofactor to detoxify cellular lipid peroxidation. Targeting GPX4 in cancer could be a promising strategy to induce ferroptosis and kill drugresistant cancers effectively. Currently, research on GPX4 inhibitors is of increasing interest in the field of anti-tumor agents. Many reviews have summarized the regulation and ferroptosis induction of GPX4 in human cancer and disease. However, insufficient attention has been paid to GPX4 inhibitors. This article outlines the molecular structures and development prospects of GPX4 inhibitors as novel anticancer agents.

铁变态反应是一种新型的程序性细胞死亡,它依赖于细胞内铁的积累,并导致有毒脂质过氧化物的增加。谷胱甘肽过氧化物酶4(GPX4)是铁变态反应的一个重要调节因子,它利用谷胱甘肽作为辅助因子对细胞脂质过氧化物进行解毒。在癌症中靶向 GPX4 可能是诱导铁变态反应并有效杀死耐药性癌症的一种有前途的策略。目前,有关 GPX4 抑制剂的研究在抗肿瘤药物领域越来越受到关注。许多综述总结了 GPX4 在人类癌症和疾病中的调控和铁氧化诱导作用。然而,人们对 GPX4 抑制剂的关注还不够。本文概述了 GPX4 抑制剂作为新型抗癌药物的分子结构和发展前景。
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引用次数: 0
A Review of the Protective Effects of Alkaloids against Alpha-synuclein Toxicity in Parkinson's Disease. 回顾生物碱对帕金森病阿尔法-突触核蛋白毒性的保护作用
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575306884240604065754
Mahdi Khodadadi, Behjat Javadi

Background: Alpha-synuclein (α-syn) aggregation products may cause neural injury and several neurodegenerative disorders (NDs) known as α-synucleinopathies. Alkaloids are secondary metabolites present in a variety of plant species and may positively affect human health, particularly α-synucleinopathy-associated NDs.

Aim: To summarize the latest scientific data on the inhibitory properties of alkaloids in α- synucleinopathies, especially in Parkinson's disease.

Methods: Literature search was performed using web-based databases including Web of Science, PubMed, and Scopus up to January 2024, in the English language.

Results: Harmala alkaloids, caffein, lycorine, piperin, acetylcorynoline, berberin, papaverine, squalamine, trodusquemine and nicotin have been found to be the most active natural alkaloids against synucleinopathy. The underlying mechanisms that contribute to this effect would be the inhibition of α-syn aggregation; elimination of formed aggregates; improvement in autophagy activation; promotion of the activity and expression of antioxidative enzymes; and prevention of oxidative injury and apoptosis in dopaminergic neurons.

Conclusion: The findings of the present study highlight the inhibitory activities of alkaloids against synucleinopathy. However, no clinical data supports the reported activities in humans, which calls attention to the need for conducting clinical trials to elucidate the efficacy, safety, proper dosage, unwanted effects and pharmacokinetics aspects of alkaloids in humans.

背景:α-突触核蛋白(α-syn)的聚集产物可能导致神经损伤和多种神经退行性疾病(NDs),这些疾病被称为α-突触核蛋白病。生物碱是存在于多种植物物种中的次级代谢产物,可能对人类健康产生积极影响,尤其是与α-突触核蛋白病相关的NDs。目的:总结生物碱在α-突触核蛋白病(尤其是帕金森病)中的抑制特性的最新科学数据:方法:使用网络数据库(包括 Web of Science、PubMed 和 Scopus)对截至 2024 年 1 月的英文文献进行检索:结果:研究发现,Harmala 生物碱、咖啡碱、番荔枝碱、哌啶、乙酰毛果芸香碱、小檗碱、木瓜碱、角鲨胺、trodusquemine 和烟碱是对突触核素病最有效的天然生物碱。产生这种作用的基本机制是抑制α-syn的聚集;消除已形成的聚集体;改善自噬激活;促进抗氧化酶的活性和表达;防止氧化损伤和多巴胺能神经元的凋亡:本研究结果突出了生物碱对突触核蛋白病的抑制作用。结论:本研究结果突出了生物碱对突触核蛋白病的抑制活性,但没有临床数据支持所报告的人体活性,因此需要进行临床试验,以阐明生物碱对人体的疗效、安全性、适当剂量、副作用和药代动力学等方面。
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引用次数: 0
Development of Mycobacterium tuberculosis Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review. 结核分枝杆菌烯酰乙酰还原酶 (InhA) 抑制剂的开发:微型综述。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575309785240902102421
Navin Kumar Tailor, Geeta Deswal, Kumar Guarve, Ajmer Singh Grewal

This review article delves into the critical role of Enoyl acyl carrier protein reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

这篇综述文章深入探讨了乙酰酰基载体蛋白还原酶(InhA;ENR)的关键作用,它是依赖 NADH 的酰基载体蛋白还原酶家族中的一种重要酶,强调了它在脂肪酸合成中的重要作用,更具体地说,是在霉菌酸的生物合成中的重要作用。本文献综述的主要目的是阐明以抑制 InhA 为目标的各种支架及其发展过程,从而破坏霉菌酸的生物合成。我们系统地探讨了硫脲、哌嗪、噻二唑、三唑、喹唑啉、苯甲酰胺、罗丹宁、苯并恶唑和吡啶等各种支架作为 InhA 抑制剂的潜力。值得注意的是,噻二唑和三唑衍生物在纳摩尔浓度范围内显示出良好的 IC50 值。该综述对 InhA 的结构、结构-活性关系提供了全面的见解,并详细概述了作为 InhA 有效抑制剂的不同支架。
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引用次数: 0
The Development History, Structural Composition, and Functions of Influenza Viruses and the Progress of Influenza Virus Inhibitors in Clinics and Clinical Trials. 流感病毒的发展历史、结构组成和功能以及流感病毒抑制剂在临床和临床试验中的进展。
IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-01 DOI: 10.2174/0113895575316416240724043949
Jianping Yong, Shaoji Lu, Canzhong Lu, Ruiwen Huang

Flu is an acute respiratory disease caused by influenza viruses. The influenza viruses are classified as Alphainfluenzavirus (influenza A virus, IAV), Betainfluenzavirus (influenza B virus, IBV), Gammainfluenzavirus (influenza C virus, ICV), and Deltainfluenzavirus (influenza D virus, IDV) according to the antigenicity of nucleoproteins (NPs) and matrix (M) proteins in vivo. It is estimated that the seasonal influenza epidemics will cause about 3-5 million cases of serious illness and 290,000-650,000 deaths in the world every year, while influenza A virus is the leading cause of infection and death. Neuraminidase (NA) is one of the most critical targets for the development of anti-influenza virus drugs, and the main drugs clinically applied for the treatment of flu are neuraminidase inhibitors. However, various mutant strains have developed resistance to these inhibitors (For example, the substrains of H274Y in H1N1, H5N1, and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new substrains emerge constantly, and the pandemics caused by the new substrains will break out at any time. Therefore, it is urgent to develop new and wide-spectrum influenza virus inhibitors for overcoming the emerging influenza pandemic. Here, we focus on describing the progress of influenza virus inhibitors in clinics and clinical trials to provide a comprehensive reference for the researchers.

流感是由流感病毒引起的一种急性呼吸道疾病。根据核蛋白(NPs)和基质蛋白(M)在体内的抗原性,流感病毒可分为甲型流感病毒(Alphainfluenzavirus,IAV)、乙型流感病毒(Betainfluenzavirus,IBV)、丙型流感病毒(Gammainfluenzavirus,ICV)和丁型流感病毒(Deltainfluenzavirus,IDV)。据估计,季节性流感流行每年将在全球造成约 300-500 万例重症病例和 29 万-65 万人死亡,而甲型流感病毒是感染和死亡的主要原因。神经氨酸酶(NA)是开发抗流感病毒药物的最关键靶点之一,临床上应用于治疗流感的主要药物是神经氨酸酶抑制剂。然而,各种变异株对这些抑制剂产生了抗药性(例如,H1N1、H5N1 中的 H274Y 子株和 H3N2 中的 E119V 子株对奥司他韦产生了抗药性)。流感病毒变异频繁,新的亚型不断出现,新亚型引起的大流行随时会爆发。因此,开发新型广谱流感病毒抑制剂以应对新出现的流感大流行迫在眉睫。在此,我们重点介绍流感病毒抑制剂在临床和临床试验方面的进展,为研究人员提供全面的参考。
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