antivirals

抗病毒药物
  • 文章类型: Journal Article
    尼帕病毒(NiV)是一种新兴的病原体,可引起脑炎,并在受感染的受试者中引起高死亡率。本系统综述旨在全面分析NiV的全球流行病学和研究进展,以确定文献中的关键知识空白。使用文献数据库搜索的文章,即PubMed,Scopus,WebofScience,和科学直接发表了5596篇文章。文章筛选后,本系统综述共包括97篇文章,包括41项流行病学研究和56项关于NiV的研究进展。大多数NiV流行病学研究是在孟加拉国进行的,反映了该国NiV爆发的沉重负担。1998年在马来西亚发现了最初的NiV爆发,随后在孟加拉国报告了爆发,印度,和菲律宾。传输路线因国家而异,主要通过马来西亚的猪,孟加拉国的椰枣汁消费,和人对人在印度。然而,NiV基因组序列的可用性仍然有限,特别是来自马来西亚和印度。死亡率也因国家而异,孟加拉国超过70%,印度,菲律宾,马来西亚不到40%。了解各国死亡率的差异对于通报NiV流行病学和加强疫情预防和管理策略至关重要。在研究发展方面,大多数研究集中在疫苗开发上,其次是系统发育分析和抗病毒研究。虽然许多疫苗和抗病毒药物在动物模型中表现出完全的保护作用,只有两种疫苗进入临床试验。系统发育分析揭示了马来西亚NiV之间的不同进化枝,NiV孟加拉国,和NiV印度,提议将NiV印度归类为与NiV孟加拉国分开的菌株。一起来看,整合疾病监测和研究的全面OneHealth方法对于未来的NiV研究至关重要。扩展NiV基因组序列的数据集,特别是来自马来西亚,孟加拉国,印度将是关键。这些研究工作对于提高我们对NiV致病性的理解和开发强大的诊断分析至关重要。有效准备和应对未来NiV爆发所需的疫苗和治疗。
    Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects. This systematic review aimed to comprehensively analyze the global epidemiology and research advancements of NiV to identify the key knowledge gaps in the literature. Articles searched using literature databases, namely PubMed, Scopus, Web of Science, and Science Direct yielded 5,596 articles. After article screening, 97 articles were included in this systematic review, comprising 41 epidemiological studies and 56 research developments on NiV. The majority of the NiV epidemiological studies were conducted in Bangladesh, reflecting the country\'s significant burden of NiV outbreaks. The initial NiV outbreak was identified in Malaysia in 1998, with subsequent outbreaks reported in Bangladesh, India, and the Philippines. Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India. However, the availability of NiV genome sequences remains limited, particularly from Malaysia and India. Mortality rates also vary according to the country, exceeding 70% in Bangladesh, India, and the Philippines, and less than 40% in Malaysia. Understanding these differences in mortality rate among countries is crucial for informing NiV epidemiology and enhancing outbreak prevention and management strategies. In terms of research developments, the majority of studies focused on vaccine development, followed by phylogenetic analysis and antiviral research. While many vaccines and antivirals have demonstrated complete protection in animal models, only two vaccines have progressed to clinical trials. Phylogenetic analyses have revealed distinct clades between NiV Malaysia, NiV Bangladesh, and NiV India, with proposals to classify NiV India as a separate strain from NiV Bangladesh. Taken together, comprehensive OneHealth approaches integrating disease surveillance and research are imperative for future NiV studies. Expanding the dataset of NiV genome sequences, particularly from Malaysia, Bangladesh, and India will be pivotal. These research efforts are essential for advancing our understanding of NiV pathogenicity and for developing robust diagnostic assays, vaccines and therapeutics necessary for effective preparedness and response to future NiV outbreaks.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)的监测已被证明可以增加早期发现的肿瘤比例和接受治愈性治疗的机会,降低死亡率约30%。
    目前的建议包括对肝硬化患者和慢性病毒性肝炎患者的特定亚组进行半年一次腹部超声检查,包括或不包括血清甲胎蛋白测量。抗病毒治疗,如nucleot(s)ide类似物,有效抑制乙型肝炎病毒(HBV)的复制和直接作用的抗病毒药物能够消除丙型肝炎病毒(HCV)在>90%的患者,从根本上改变了病毒性肝病的结果,但没有消除,肝硬化和非肝硬化患者肝癌的风险。HCC风险是实施具有成本效益的监测的关键起点,也应指导有关其方式的决策过程。随着全球有效治疗的病毒患者数量不断增加,迫切需要确定监测的利弊比对谁有利,并确定如何对此类患者进行具有成本效益的筛查。
    本文讨论了这一主题,并试图确定哪些患者应在HBV抑制或HCV根除后继续进行HCC监测,基于成本效益原则和HCC风险随时间下降的事实。我们还制定了一项监测算法的建议,该算法将HCC的监测使用从“一刀切”方法转换为基于肿瘤风险(精确监测)的个性化计划。
    UNASSIGNED: Surveillance for hepatocellular carcinoma (HCC) has been proven to increase the proportion of tumors detected at early stages and the chance of receiving curative therapies, reducing mortality by about 30%.
    UNASSIGNED: Current recommendations consist of a semi-annual abdominal ultrasound with or without serum alpha-fetoprotein measurement in patients with cirrhosis and specific subgroups of populations with chronic viral hepatitis. Antiviral therapies, such as nucleot(s)ide analogs that efficiently suppress the replication of hepatitis B virus (HBV) and direct-acting antiviral drugs able to eliminate the hepatitis C virus (HCV) in >90% of patients, have radically changed the outcomes of viral liver disease and decreased, but not eliminated, the risk of HCC in both cirrhotic and non-cirrhotic patients. HCC risk is a key starting point for implementing a cost-effective surveillance and should also guide the decision-making process concerning its modality. As the global number of effectively treated viral patients continues to rise, there is a pressing need to identify those for whom the benefit-to-harm ratio of surveillance is favorable and to determine how to conduct cost-effective screening on such patients.
    UNASSIGNED: This article addresses this topic and attempts to determine which patients should continue HCC surveillance after HBV suppression or HCV eradication, based on cost-effectiveness principles and the fact that HCC risk declines over time. We also formulate a proposal for a surveillance algorithm that switches the use of surveillance for HCC from the \"one-size-fits-all\" approach to individualized programs based on oncologic risk (precision surveillance).
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  • 文章类型: Journal Article
    人巨细胞病毒是一种与人类共同进化的古老病毒。它在没有疫苗接种或治愈的可疑个体中建立了终身感染。该病毒可以在血清反应阳性的孕妇中传播给发育中的胎儿,它是先天性传染病的主要原因。虽然大多数受感染的婴儿在出生时仍然无症状,先天性巨细胞病毒感染可导致幸存者长期严重的神经发育障碍,造成相当大的经济和社会困难。关于巨细胞病毒病理生理学和病毒复制周期的最新发现可能有助于创新诊断和治疗的发展。包括有效的疫苗。这篇综述将详细介绍我们对人类巨细胞病毒感染的理解,关于有助于其病理生理学的病毒基因组和转录组的深入讨论。新生儿的临床过程也将被强调,包括产妇和新生儿检查,治疗建议,和长期结果。
    Human cytomegalovirus is an ancient virus that has co-evolved with humans. It establishes a life-long infection in suspectable individuals for which there is no vaccination or cure. The virus can be transmitted to a developing fetus in seropositive pregnant women, and it is the leading cause of congenital infectious disease. While the majority of infected infants remain asymptomatic at birth, congenital cytomegalovirus infection can lead to substantial long-term neurodevelopmental impairments in survivors, resulting in considerable economic and social hardships. Recent discoveries regarding cytomegalovirus pathophysiology and viral replication cycles might enable the development of innovative diagnostics and therapeutics, including an effective vaccine. This Review will detail our understanding of human cytomegalovirus infection, with an in-depth discussion regarding the viral genome and transcriptome that contributes to its pathophysiology. The neonate\'s clinical course will also be highlighted, including maternal and neonatal testing, treatment recommendations, and long-term outcomes.
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  • 文章类型: Journal Article
    解决怀孕期间管理病毒感染的复杂性对于明智的医疗决策至关重要。这篇全面的综述深入探讨了影响孕妇的关键病毒感染的管理,即人类免疫缺陷病毒(HIV),乙型肝炎病毒/丙型肝炎病毒(HBV/HCV),流感,巨细胞病毒(CMV),和SARS-CoV-2(COVID-19)。我们评估了每种感染的抗病毒治疗的安全性和有效性,同时还探索创新途径,如基因疫苗及其在减轻怀孕期间病毒威胁方面的潜力。此外,审查审查了克服挑战的策略,包括预防性和治疗性疫苗研究,监管方面的考虑,和安全协议。利用先进的方法,包括PBPK建模,机器学习,人工智能,和因果推断,我们可以在这个复杂的领域中增强我们的理解力和决策能力。这篇叙述性评论旨在阐明不同的方法和正在进行的进步,这篇综述旨在促进孕妇抗病毒治疗的进展,改善产妇和胎儿的健康结局。
    Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.
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  • 文章类型: Journal Article
    严重急性呼吸系统综合症冠状病毒2型(SARS-CoV-2)由于其进化和产生新的亚变体的能力,仍然是全球威胁,导致新的感染浪潮.此外,其他冠状病毒,如中东呼吸综合征冠状病毒(MERS-CoV,以前称为hCoV-EMC),这种疾病于2012年首次出现,持续存在并继续对人类构成严重疾病的威胁。新型冠状病毒的持续鉴定,加上不同菌株之间遗传重组的潜力,增加了全球关注的新型冠状病毒进化枝出现的可能性。因此,迫切需要pan-CoV治疗药物和疫苗。在HCV蛋白酶抑制剂筛选的广泛优化之后,发现了一种新型3CLPro抑制剂(MK-7845),随后进行了分析.MK-7845表现出针对一组临床SARS-CoV-2亚变体和MERS-CoV的具有广谱活性的纳摩尔体外效力。此外,口服时,在感染SARS-CoV-2(K18-hACE2小鼠)和MERS-CoV(K18-hDDP4小鼠)的转基因小鼠的肺中,MK-7845显示病毒负荷显著降低>6个对数数量级。
    Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).
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  • 文章类型: Journal Article
    如今,细菌和病毒来源的传染病代表了世界范围内的严重医学问题。事实上,抗生素耐药性的发展是导致细菌菌株出现的原因,这些菌株甚至对新型抗生素也是难以抵抗的。此外,最近的COVID-19大流行表明,新病毒可能会出现并在世界各地传播。传染病的增加取决于多种因素,包括营养不良,人口从发展中国家大量迁移到工业化地区,和人类微生物群的改变。已经深入探索了常规抗生素和抗病毒药物的替代疗法。在这方面,植物和海洋生物是产品的巨大来源,如多酚,生物碱,羊毛硫肽,和萜类化合物,具有抗菌和抗病毒活性。它们的主要作用机制涉及细菌细胞膜的修饰,随着孔隙的形成,细胞内容的释放,以及抑制细菌对宿主细胞的粘附,以及外排泵。天然抗病毒药物可以干扰病毒复制和传播,通过增强干扰素的产生来保护宿主。值得注意的是,这些抗病毒药物并非没有副作用,它们对人类的管理需要更多的安全性研究。天然抗菌和抗病毒化合物的临床前研究证实了它们对细菌和病毒的作用,但仍然只有少数临床试验。因此,它们的充分开发和更深入的临床研究代表了医学领域的下一步。
    Nowadays, infectious diseases of bacterial and viral origins represent a serious medical problem worldwide. In fact, the development of antibiotic resistance is responsible for the emergence of bacterial strains that are refractory even to new classes of antibiotics. Furthermore, the recent COVID-19 pandemic suggests that new viruses can emerge and spread all over the world. The increase in infectious diseases depends on multiple factors, including malnutrition, massive migration of population from developing to industrialized areas, and alteration of the human microbiota. Alternative treatments to conventional antibiotics and antiviral drugs have intensively been explored. In this regard, plants and marine organisms represent an immense source of products, such as polyphenols, alkaloids, lanthipeptides, and terpenoids, which possess antibacterial and antiviral activities. Their main mechanisms of action involve modifications of bacterial cell membranes, with the formation of pores, the release of cellular content, and the inhibition of bacterial adherence to host cells, as well as of the efflux pump. Natural antivirals can interfere with viral replication and spreading, protecting the host with the enhanced production of interferon. Of note, these antivirals are not free of side effects, and their administration to humans needs more research in terms of safety. Preclinical research with natural antibacterial and antiviral compounds confirms their effects against bacteria and viruses, but there are still only a few clinical trials. Therefore, their full exploitation and more intensive clinical studies represent the next steps to be pursued in this area of medicine.
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  • 文章类型: Journal Article
    研究了从远东太平洋沿岸各个红藻家族分离的硫酸化多糖对人类免疫缺陷病毒1(HIV-1)的抑制作用。来自Chondrusarmatus的κ和λ-角叉菜胶的抗HIV-1活性,发现了原始的高度硫酸化的X-角叉菜胶,其中3,6-脱水半乳糖含量低,来自Tichocarpuscrinitus和i/κ-角叉菜胶,具有杂化结构,从松弛的白蚁中分离。将这些多糖及其低重量寡糖的抗病毒作用与市售κ-角叉菜胶进行了比较。在这里,我们使用了基于HIV-1的慢病毒颗粒,并评估了这些角叉菜胶在无毒浓度下显着抑制具有不同包膜蛋白假型化的慢病毒颗粒的转导潜力。靶向神经元或T细胞来源的细胞。使用编码标记eGFP蛋白的嵌合复制能力Mo-MuLV(莫洛尼鼠白血病逆转录病毒)证实这些角叉菜胶的抗病毒作用。我们发现来自T.crinitus的X-角叉菜胶及其低重量衍生物和来自C.armatus的λ-角叉菜胶有效地抑制由逆转录病毒引起的感染。获得的数据表明,角叉菜胶对基于HIV-1的慢病毒颗粒的转导效率的抑制作用的差异可能与所研究的多糖的结构特征有关。
    The efficiency of human immunodeficiency virus-1 (HIV-1) inhibition by sulfated polysaccharides isolated from the various families of red algae of the Far East Pacific coast were studied. The anti-HIV-1 activity of kappa and lambda-carrageenans from Chondrus armatus, original highly sulfated X-carrageenan with low content of 3,6-anhydrogalactose from Tichocarpus crinitus and i/κ-carrageenan with hybrid structure isolated from Ahnfeltiopsis flabelliformis was found. The antiviral action of these polysaccharides and its low-weight oligosaccharide was compared with commercial κ-carrageenan. Here we used the HIV-1-based lentiviral particles and evaluated that these carrageenans in non-toxic concentrations significantly suppress the transduction potential of lentiviral particles pseudotyped with different envelope proteins, targeting cells of neuronal or T-cell origin. The antiviral action of these carrageenans was confirmed using the chimeric replication competent Mo-MuLV (Moloney murine leukemia retrovirus) encoding marker eGFP protein. We found that X-carrageenans from T. crinitus and its low weight derivative and λ-carrageenan from C. armatus effectively suppress the infection caused by retrovirus. The obtained data suggest that the differences in the suppressive effect of carrageenans on the transduction efficiency of HIV-1 based lentiviral particles may be related to the structural features of the studied polysaccharides.
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  • 文章类型: Journal Article
    SARS-CoV-2于2019年首次发现,并已在全球范围内传播到大流行水平,造成重大的健康和经济负担。尽管已经开发了针对SARS-CoV-2的疫苗,其长期疗效和特异性尚未确定,抗病毒药物仍然是必要的。黄酮类化合物,常见于植物中,水果,和蔬菜,是人类饮食的一部分,由于其抗病毒和抗微生物活性以及对其他生物活性的影响,作为潜在的治疗剂引起了相当大的关注,比如炎症。本研究采用生化结合,细胞,分子动力学,和分子对接实验提供了令人信服的证据,证明类黄酮木犀草素(2-(3,4-二羟苯基)-5,7-二羟基-4H-色烯-4-酮)具有抗SARS-CoV-23-胰凝乳蛋白酶样蛋白酶(3CLpro)的抗病毒活性,锌,和维生素C。木犀草素对2µM3CLpro的IC50为78µM,在锌存在下降低10倍至7.6µM,镁,和维生素C。热力学稳定性分析表明木犀草素对3CLpro的结构影响最小,而金属离子和维生素C显著改变蛋白酶的热力学稳定性。相互作用组分析发现潜在的宿主病毒相互作用和与木犀草素活性相关的功能簇,支持这种黄酮在对抗SARS-CoV-2感染中的相关性。这项全面的研究揭示了木犀草素的治疗潜力,并提供了对其对抗SARS-CoV-2作用机制的见解。木犀草素的新配方,镁,锌,维生素C可能是治疗COVID-19患者的有效途径。
    SARS-CoV-2 was first discovered in 2019 and has disseminated throughout the globe to pandemic levels, imposing significant health and economic burdens. Although vaccines against SARS-CoV-2 have been developed, their long-term efficacy and specificity have not been determined, and antiviral drugs remain necessary. Flavonoids, which are commonly found in plants, fruits, and vegetables and are part of the human diet, have attracted considerable attention as potential therapeutic agents due to their antiviral and antimicrobial activities and effects on other biological activities, such as inflammation. The present study uses a combination of biochemical, cellular, molecular dynamics, and molecular docking experiments to provide compelling evidence that the flavonoid luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one) has antiviral activity against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) that is synergistically enhanced by magnesium, zinc, and vitamin C. The IC50 of luteolin against 2 µM 3CLpro is 78 µM and decreases 10-fold to 7.6 µM in the presence of zinc, magnesium, and vitamin C. Thermodynamic stability analyses revealed that luteolin has minimal effects on the structure of 3CLpro, whereas metal ions and vitamin C significantly alter the thermodynamic stability of the protease. Interactome analysis uncovered potential host-virus interactions and functional clusters associated with luteolin activity, supporting the relevance of this flavone for combating SARS-CoV-2 infection. This comprehensive investigation sheds light on luteolin\'s therapeutic potential and provides insights into its mechanisms of action against SARS-CoV-2. The novel formulation of luteolin, magnesium, zinc, and vitamin C may be an effective avenue for treating COVID-19 patients.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    越来越多的全球研究集中在开发新的治疗方法,以对抗抗微生物和抗病毒耐药性。开心果是很好的蛋白质来源,纤维,单不饱和脂肪酸,矿物,维生素,和植物化学物质(类胡萝卜素,酚酸,类黄酮和花青素)。在开心果中发现的植物化学物质是结构多样的化合物,具有抗菌和抗病毒的潜力,表现为单个化合物,提取物并复合成纳米颗粒。还报道了与现有药物组合的协同作用。在这里,我们报告了开心果的抗菌和抗病毒潜力的概述:研究表明,革兰氏阳性细菌菌株,如金黄色葡萄球菌,是细菌中最敏感的,而抗病毒作用已报道针对单纯疱疹病毒1(HSV-1)。在已知的开心果化合物中,玉米黄质已被证明会影响人细胞的HSV-1附着穿透和病毒DNA合成。这些数据表明开心果提取物和衍生物可用于金黄色葡萄球菌皮肤感染和眼部疱疹感染的局部治疗。
    Increased global research is focused on the development of novel therapeutics to combat antimicrobial and antiviral resistance. Pistachio nuts represent a good source of protein, fiber, monounsaturated fatty acids, minerals, vitamins, and phytochemicals (carotenoids, phenolic acids, flavonoids and anthocyanins). The phytochemicals found in pistachios are structurally diverse compounds with antimicrobial and antiviral potential, demonstrated as individual compounds, extracts and complexed into nanoparticles. Synergistic effects have also been reported in combination with existing drugs. Here we report an overview of the antimicrobial and antiviral potential of pistachio nuts: studies show that Gram-positive bacterial strains, such as Staphylococcus aureus, are the most susceptible amongst bacteria, whereas antiviral effect has been reported against herpes simplex virus 1 (HSV-1). Amongst the known pistachio compounds, zeaxanthin has been shown to affect both HSV-1 attachment penetration of human cells and viral DNA synthesis. These data suggest that pistachio extracts and derivatives could be used for the topical treatment of S. aureus skin infections and ocular herpes infections.
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