Secondary metabolism

次级代谢
  • 文章类型: Journal Article
    干旱期间气孔关闭会抑制碳吸收,并可能降低树木的防御能力。干旱期间有限的碳供应可能会增加树木的死亡风险,特别是如果干旱限制了树木在生物攻击期间迅速产生防御的能力。我们使用实验干旱下成熟松果中模拟树皮甲虫攻击前后的碳储量和化学防御的生理数据,对针叶树防御的新模型进行了参数化。使用一致的青蒿素真菌(Ophiostomasp。)Ipsconfuss,主要树皮甲虫在这棵树上定居,引起防御性反应。碳储量较多的树木产生了更多的防御能力,但测得的韧皮部碳储量仅占c。引起的防御反应的23%。我们的模型预测了如果仅当地储备就支持国防生产的普遍死亡率,建议将储存的树脂或碳储备大量重新动员和运输到接种部位。我们的结果表明,真菌接种后,从头萜烯的合成仅占毛果的总韧皮部萜烯的一部分。没有直接将韧皮部萜烯浓度归因于可用碳,许多研究可能高估了树诱导的防御反应中从头合成萜烯的规模和重要性。
    Stomatal closure during drought inhibits carbon uptake and may reduce a tree\'s defensive capacity. Limited carbon availability during drought may increase a tree\'s mortality risk, particularly if drought constrains trees\' capacity to rapidly produce defenses during biotic attack. We parameterized a new model of conifer defense using physiological data on carbon reserves and chemical defenses before and after a simulated bark beetle attack in mature Pinus edulis under experimental drought. Attack was simulated using inoculations with a consistent bluestain fungus (Ophiostoma sp.) of Ips confusus, the main bark beetle colonizing this tree, to induce a defensive response. Trees with more carbon reserves produced more defenses but measured phloem carbon reserves only accounted for c. 23% of the induced defensive response. Our model predicted universal mortality if local reserves alone supported defense production, suggesting substantial remobilization and transport of stored resin or carbon reserves to the inoculation site. Our results show that de novo terpene synthesis represents only a fraction of the total measured phloem terpenes in P. edulis following fungal inoculation. Without direct attribution of phloem terpene concentrations to available carbon, many studies may be overestimating the scale and importance of de novo terpene synthesis in a tree\'s induced defense response.
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  • 文章类型: Journal Article
    真正的羊肚菌(羊肚菌)是全球知名的药用和食用蘑菇。由真菌引起的白霉菌病是羊肚菌的主要病害,具有发生率广、破坏性强的特点。在不同病原体的分离率中观察到的差异表明它们不同程度的宿主适应性和竞争生存能力。为了阐明其潜在的机制,这项研究,大方县白霉菌病的病原,贵州省被分离纯化,通过形态学鉴定为长孢子假孢子,分子生物学和致病性测试。此外,长孢子菌的高质量基因组(40.846Mb)组装的N50为3.09Mb,预测7381个蛋白质编码基因。单拷贝同源基因的系统发育分析表明,长尾孢霉和青发斑霉具有最密切的进化关系,分叉成两个分支,大约50(44.3-61.4)个MYA。此外,与引起羊肚菌病的其他两种病原体相比,Z.penicillatusandcladobotryumprotossum,发现它们具有相似比例的碳水化合物酶类型,并编码丰富的细胞壁降解酶,如几丁质酶和葡聚糖酶,表明它们在疾病发展中的重要作用。此外,长孢子虫和Z.penicillatus的次生代谢基因簇与亮氨酸抑制素A和亮氨酸抑制素B(peptaibol)显示出高度的相似性。此外,还在长孢霉和突出梭菌中鉴定出具有合成毒性物质OchratoxinA的基因簇,表明它们可能对食品安全构成潜在威胁。这项研究提供了对长孢子假单胞菌基因组的有价值的见解,有助于致病性研究。
    True morels (Morchella) are globally renowned medicinal and edible mushrooms. White mold disease caused by fungi is the main disease of Morchella, which has the characteristics of wide incidence and strong destructiveness. The disparities observed in the isolation rates of different pathogens indicate their varying degrees of host adaptability and competitive survival abilities. In order to elucidate its potential mechanism, this study, the pathogen of white mold disease from Dafang county, Guizhou Province was isolated and purified, identified as Pseudodiploöspora longispora by morphological, molecular biological and pathogenicity tests. Furthermore, high-quality genome of P. longisporus (40.846 Mb) was assembled N50 of 3.09 Mb, predicts 7381 protein-coding genes. Phylogenetic analysis of single-copy homologous genes showed that P. longispora and Zelopaecilomyces penicillatus have the closest evolutionary relationship, diverging into two branches approximately 50 (44.3-61.4) MYA. Additionally, compared with the other two pathogens causing Morchella disease, Z. penicillatus and Cladobotryum protrusum, it was found that they had similar proportions of carbohydrate enzyme types and encoded abundant cell wall degrading enzymes, such as chitinase and glucanase, indicating their important role in disease development. Moreover, the secondary metabolite gene clusters of P. longispora and Z. penicillatus show a high degree of similarity to leucinostatin A and leucinostatin B (peptaibols). Furthermore, a gene cluster with synthetic toxic substance Ochratoxin A was also identified in P. longispora and C. protrusum, indicating that they may pose a potential threat to food safety. This study provides valuable insights into the genome of P. longispora, contributing to pathogenicity research.
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  • 文章类型: Journal Article
    真菌Nodorum在小麦上引起septorianodorum斑点。本文研究了真菌Velvet家族转录因子VeA在P.nodorum发育和毒力中的作用。删除P.nodorumVea直系同源物,PnVea,导致生长异常,包括色素沉着,废除了无性孢子形成,对小麦的毒力大大降低。比较RNA-Seq和RT-PCR分析显示,PnVeA的缺失也使主要坏死营养效应基因的表达解耦。此外,PnVeA的缺失导致4个预测的次级代谢产物(SM)基因簇的上调。使用液相色谱质谱,观察到SM基因簇之一导致霉菌毒素交替醇的积累。PnVeA对于无性孢子形成至关重要,全毒力,次生代谢和坏死效应调节。
    The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation.
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  • 文章类型: Journal Article
    假单胞菌蛋白原通常可以产生多种抗生素,包括pytouteorin(Plt),2,4-二乙酰间苯三酚(DAPG),和吡咯腈(Prn)。在这项研究中,我们发现并表征了群体感应(QS)系统,PpqI/R,在P.蛋白原H78。PpqI/R,由P.protogensH78基因组中的两个开放阅读框(ORF)(H78_01960/01961)编码,是一个LuxI/R型QS系统。四种长链酰基高丝氨酸内酯(AHL)信号分子,3-OH-C10-HSL,3-OH-C12-HSL,C12-HSL,和3-OH-C14-HSL,由H78生产。这些AHL的生物合成由PpqI合酶催化,并在异源表达时在H78和大肠杆菌中被PpqR调节剂激活。PpqR通过与相应的AHL合作靶向ppqI启动子上游的lux盒激活ppqI表达。上述四种AHLs表现出不同的诱导ppqI启动子表达的能力,3-OH-C12-HSL显示出最高的诱导活性。在H78细胞中,ppqI/R表达被两组分系统GacS/A和RNA分子伴侣Hfq激活。次级代谢中PpqI/R系统的差异调节对DAPG生物合成和ped操纵子(参与挥发性有机化合物生物合成)的表达有负面影响。相比之下,Plt生物合成和prn操纵子表达受PpqI/R正调控。总之,PpqI/R,蛋白质原P.中第一个表征的QS系统,被GacS/A和Hfq激活,并控制次级代谢产物的表达,包括抗生素。
    Pseudomonas protegens can generally produce multiple antibiotics including pyoluteorin (Plt), 2,4-diacetylphloroglucinol (DAPG), and pyrrolnitrin (Prn). In this study, we discovered and characterized a quorum sensing (QS) system, PpqI/R, in P. protegens H78. PpqI/R, encoded by two open reading frames (ORFs) (H78_01960/01961) in P. protegens H78 genome, is a LuxI/R-type QS system. Four long-chain acyl homoserine lactone (AHL) signaling molecules, 3-OH-C10-HSL, 3-OH-C12-HSL, C12-HSL, and 3-OH-C14-HSL, are produced by H78. Biosynthesis of these AHLs is catalyzed by PpqI synthase and activated by the PpqR regulator in H78 and in Escherichia coli when heterologously expressed. PpqR activates ppqI expression by targeting the lux box upstream of the ppqI promoter in cooperation with corresponding AHLs. The four aforementioned AHLs exhibited different capabilities to induce ppqI promoter expression, with 3-OH-C12-HSL showing the highest induction activity. In H78 cells, ppqI/R expression is activated by the two-component system GacS/A and the RNA chaperone Hfq. Differential regulation of the PpqI/R system in secondary metabolism has a negative effect on DAPG biosynthesis and ped operon (involved in volatile organic compound biosynthesis) expression. In contrast, Plt biosynthesis and prn operon expression were positively regulated by PpqI/R. In summary, PpqI/R, the first characterized QS system in P. protegens, is activated by GacS/A and Hfq and controls the expression of secondary metabolites, including antibiotics.
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  • 文章类型: Journal Article
    多酚是天然化合物,是基于植物的生物活性分子,近年来,人们越来越感兴趣。以多个品种为特征,多酚主要存在于水果和蔬菜中。目前,许多疾病正在等待治愈或缓解症状的解决方案。然而,药物或其他化学策略在使用治疗剂或许多疾病的静止检测工具时具有局限性,因此,研究人员仍然需要研究预防或改进治疗方法。因此,阐明多酚是有意义的,它们的生物活性效应,补充,和消费。多酚的缺点是它们具有有限的生物利用度,尽管它们具有多种有益的生物活性作用。在这种情况下,已经开发了几种不同的策略来提高生物利用度,特别是脂质体和纳米颗粒。由于营养是改善健康的最重要因素之一,在日常饮食中包含基于植物的分子是重要的,并且继续受到热烈的研究。营养,这对所有年龄段的人都很重要,是多酚生物活性的关键。
    Polyphenols are natural compounds which are plant-based bioactive molecules, and have been the subject of growing interest in recent years. Characterized by multiple varieties, polyphenols are mostly found in fruits and vegetables. Currently, many diseases are waiting for a cure or a solution to reduce their symptoms. However, drug or other chemical strategies have limitations for using a treatment agent or still detection tool of many diseases, and thus researchers still need to investigate preventive or improving treatment. Therefore, it is of interest to elucidate polyphenols, their bioactivity effects, supplementation, and consumption. The disadvantage of polyphenols is that they have a limited bioavailability, although they have multiple beneficial outcomes with their bioactive roles. In this context, several different strategies have been developed to improve bioavailability, particularly liposomal and nanoparticles. As nutrition is one of the most important factors in improving health, the inclusion of plant-based molecules in the daily diet is significant and continues to be enthusiastically researched. Nutrition, which is important for individuals of all ages, is the key to the bioactivity of polyphenols.
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  • 文章类型: Journal Article
    真菌产生的次生代谢产物以其生物学特性而闻名,在医学中发挥重要作用。这些代谢物有助于控制感染和治疗慢性疾病,从而大大有助于人类健康的改善。尽管知识丰富,真菌巨大的生物多样性和生物合成潜力仍未被开发,强调需要进一步研究天然产物。在这次审查中,描述了几种真菌来源的次生代谢产物,强调新颖的结构和骨架。分析系统的进步大大促进了这些代谢物的检测和表征,特别是现代液相色谱/质谱联用。这些改进主要增强了灵敏度,决议,和分析流速。由于新代谢物的体外生产通常低于已知代谢物的重新分离,了解真菌基因表达中基于染色质的改变可以阐明发现新代谢物的潜在途径。讨论了几种诱导不同菌株产生代谢物的方案,证明需要均匀的实验程序,以实现一致的生物合成活化。
    Secondary metabolites produced by fungi are well known for their biological properties, which play important roles in medicine. These metabolites aid in managing infections and treating chronic illnesses, thereby contributing substantially to human health improvement. Despite this extensive knowledge, the vast biodiversity and biosynthetic potential of fungi is still largely unexplored, highlighting the need for further research in natural products. In this review, several secondary metabolites of fungal origin are described, emphasizing novel structures and skeletons. The detection and characterization of these metabolites have been significantly facilitated by advancements in analytical systems, particularly modern hyphenated liquid chromatography/mass spectrometry. These improvements have primarily enhanced sensitivity, resolution, and analysis flow velocity. Since the in vitro production of novel metabolites is often lower than the re-isolation of known metabolites, understanding chromatin-based alterations in fungal gene expression can elucidate potential pathways for discovering new metabolites. Several protocols for inducing metabolite production from different strains are discussed, demonstrating the need for uniformity in experimental procedures to achieve consistent biosynthetic activation.
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  • 文章类型: Journal Article
    背景:Gemmatimonadota细菌在自然界中广泛分布,但人们对它们在海洋环境中的代谢潜力和生态作用知之甚少。
    结果:这里,我们获得了495个宏基因组组装基因组(MAG),和相关的病毒,从世界各地的沿海到深海沉积物。我们使用这个扩展的基因组目录来比较蛋白质组成并更新这些细菌的系统发育。海洋Gemmatimonadota在系统发育上与先前报道的陆地环境不同。这些基因组的功能分析显示这些海洋基因型能够降解复杂的有机碳,反硝化,硫酸盐还原,氧化硫化物和亚硫酸盐。有趣的是,在Gemmaatimonadota中,次级代谢物生物合成具有广泛的遗传潜力,这可能代表了新的天然产物的未开发来源。此外,与Gemmaatimonadota相关的病毒具有“劫持”和操纵宿主代谢的潜力,包括脂多糖在其宿主中的组装。
    结论:这种扩大的基因组多样性促进了我们对各种生态系统中这些全球分布细菌的理解,并揭示了陆地和海洋群落之间的遗传差异。视频摘要。
    BACKGROUND: Gemmatimonadota bacteria are widely distributed in nature, but their metabolic potential and ecological roles in marine environments are poorly understood.
    RESULTS: Here, we obtained 495 metagenome-assembled genomes (MAGs), and associated viruses, from coastal to deep-sea sediments around the world. We used this expanded genomic catalog to compare the protein composition and update the phylogeny of these bacteria. The marine Gemmatimonadota are phylogenetically different from those previously reported from terrestrial environments. Functional analyses of these genomes revealed these marine genotypes are capable of degradation of complex organic carbon, denitrification, sulfate reduction, and oxidizing sulfide and sulfite. Interestingly, there is widespread genetic potential for secondary metabolite biosynthesis across Gemmatimonadota, which may represent an unexplored source of novel natural products. Furthermore, viruses associated with Gemmatimonadota have the potential to \"hijack\" and manipulate host metabolism, including the assembly of the lipopolysaccharide in their hosts.
    CONCLUSIONS: This expanded genomic diversity advances our understanding of these globally distributed bacteria across a variety of ecosystems and reveals genetic distinctions between those in terrestrial and marine communities. Video Abstract.
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  • 文章类型: Journal Article
    Consento(CON)作为一种系统性杀真菌剂,会对环境造成重大危害,对非目标生物的健康产生不利影响。一氧化氮(NO),一个信号分子,已知在植物生理和非生物胁迫耐受性中起关键作用。然而,NO是否在小麦幼苗中发挥任何增强杀菌剂CON耐受性的作用尚不清楚。因此,我们进行了水培实验i)以研究小麦幼苗对杀菌剂CON胁迫的形态生理生化变化,和ii)检查NO和杀真菌剂CON处理对氧化损伤的影响,抗氧化系统,小麦幼苗中系统性杀菌剂的次生代谢和解毒。结果表明,CON杀菌剂在最高(4X)浓度下显著降低小麦幼苗鲜重(46.89%),枝条长度(40.26%),根长(56.11%)和总叶绿素含量(67.44%)呈剂量反应关系。此外,CON显著增加过氧化氢,丙二醛,过氧化氢酶,抗坏血酸过氧化物酶,谷胱甘肽-S-转移酶,和过氧化物酶活性,而谷胱甘肽(GSH)含量降低。这最终损害了细胞的氧化还原稳态,导致细胞膜氧化损伤。在杀菌剂处理下,NO的添加降低了杀菌剂的植物毒性,幼苗生长增加了60%以上。NO的施用减轻了CON的植物毒性,这反映在小麦叶片中叶绿素色素的显着增加(69.88%)和氧化损伤的减少。的确,NO缓解作用能够增加幼苗对杀菌剂的耐受性,导致抗氧化和解毒酶活性增加,GSH水平提高(78.54%)。有趣的是,NO通过苯丙素途径通过增强苯丙氨酸解氨酶等次级代谢酶的活性减轻CON植物毒性(47.28%),多酚氧化酶(9%),和相关代谢物,如酚酸(77.62%),小麦叶片中的黄酮类化合物(34.33%)。我们的研究提供了证据,表明NO通过增强抗氧化剂的活性在小麦中系统性杀菌剂的代谢和解毒中起关键作用。解毒和次级代谢酶。
    Consento (CON) poses a significant environmental hazard as a systemic fungicide, adversely affecting the health of non-target organisms. Nitric oxide (NO), a signaling molecule, is known to play a crucial role in plant physiology and abiotic stress tolerance. However, whether NO plays any role to enhance fungicide CON tolerance in wheat seedlings is yet unclear. Therefore, we conducted a hydroponic experiment i) to investigate the morpho-physio-biochemical changes of wheat seedlings to fungicide CON stress, and ii) to examine the effects of NO and fungicide CON treatments on oxidative damage, antioxidant system, secondary metabolism and detoxification of systemic fungicide in wheat seedlings. The results showed that CON fungicide at the highest (4X) concentration significantly decreased wheat seedlings fresh weight (46.89%), shoot length (40.26%), root length (56.11%) and total chlorophyll contents (67.44%) in a dose response relationship. Moreover, CON significantly increased hydrogen peroxide, malondialdehyde, catalase, ascorbate peroxidase, glutathione-S-transferase, and peroxidase activities while decreased reduced glutathione (GSH) content. This ultimately impaired the redox homeostasis of cells, leading to oxidative damage in cell membrane. Under fungicide treatment, the addition of NO reduced the fungicide phytotoxicity, with an increase of over 60% in seedling growth. The NO application mitigated CON phytotoxicity as reflected by significantly increased chlorophyll pigments (69.88%) and decreased oxidative damage in wheat leaves. Indeed, the NO alleviatory effect was able to increase the tolerance of seedlings to fungicide, which resulted increments in antioxidant and detoxification enzymes activity, with the enhanced GSH level (78.54%). Interestingly, NO alleviated CON phytotoxicity through the phenylpropanoid pathway by enhancing the activity of secondary metabolism enzymes such as phenylalanine ammonia-lyase (47.28%), polyphenol oxidase (9%), and associated metabolites such as phenolic acids (77.62%), flavonoids (34.33%) in wheat leaves. Our study has provided evidence that NO plays a key role in the metabolism and detoxification of systemic fungicide in wheat through enhanced activity of antioxidants, detoxifications and secondary metabolic enzymes.
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  • 文章类型: Journal Article
    果实产生种类繁多的次生代谢产物,具有很大的经济价值。代谢物的分析测量是繁琐的,耗时,而且昂贵。此外,代谢物的浓度因树而异,这使得很难选择树木来收集水果。目前的研究测试了基于深度学习的模型是否可以单独使用水果和叶子图像来预测代谢物的浓度等级(高或低)。我们从60万平方公里的野外生长的印度树收集了果实和叶子(n=1045),想象他们,并测量了五种代谢物的浓度(印字素,去乙酰-Salannin,Salannin,nimbin和nimbolide)使用高效液相色谱法。我们使用这些数据来训练用于代谢物类别预测的深度学习模型。七个测试中的最佳模型(YOLOv5、GoogLeNet、InceptionNet,EfficientNet_B0,Resnext_50,Resnet18和SqueezeNet)提供了0.93的验证F1得分和0.88的测试F1得分。在测试集中仅果实模型的敏感性和特异性分别为83.52±6.19和82.35±5.96,以及79.40±8.50和85.64±6.21,分别。低级别的灵敏度进一步提高到92.67±5.25,高级的灵敏度进一步提高到88.11±9.17,这两类的特异性都为100%,使用多分析物框架。我们将多分析物模型纳入Android移动应用程序Fruit-In-Sight中,该应用程序使用水果和叶子图像来决定是否“挑选”或“不挑选”基于代谢物浓度类别的特定树上的水果。我们的研究提供了证据,表明仅水果和叶子的图像就可以预测次生代谢物的浓度类别,而无需使用昂贵的实验室设备和繁琐的分析程序。从而简化了选择合适的树进行水果收集的过程。
    Fruits produce a wide variety of secondary metabolites of great economic value. Analytical measurement of the metabolites is tedious, time-consuming, and expensive. Additionally, metabolite concentrations vary greatly from tree to tree, making it difficult to choose trees for fruit collection. The current study tested whether deep learning-based models can be developed using fruit and leaf images alone to predict a metabolite\'s concentration class (high or low). We collected fruits and leaves (n = 1045) from neem trees grown in the wild across 0.6 million sq km, imaged them, and measured concentration of five metabolites (azadirachtin, deacetyl-salannin, salannin, nimbin and nimbolide) using high-performance liquid chromatography. We used the data to train deep learning models for metabolite class prediction. The best model out of the seven tested (YOLOv5, GoogLeNet, InceptionNet, EfficientNet_B0, Resnext_50, Resnet18, and SqueezeNet) provided a validation F1 score of 0.93 and a test F1 score of 0.88. The sensitivity and specificity of the fruit model alone in the test set were 83.52 ± 6.19 and 82.35 ± 5.96, and 79.40 ± 8.50 and 85.64 ± 6.21, for the low and the high classes, respectively. The sensitivity was further boosted to 92.67± 5.25 for the low class and 88.11 ± 9.17 for the high class, and the specificity to 100% for both classes, using a multi-analyte framework. We incorporated the multi-analyte model in an Android mobile App Fruit-In-Sight that uses fruit and leaf images to decide whether to \'pick\' or \'not pick\' the fruits from a specific tree based on the metabolite concentration class. Our study provides evidence that images of fruits and leaves alone can predict the concentration class of a secondary metabolite without using expensive laboratory equipment and cumbersome analytical procedures, thus simplifying the process of choosing the right tree for fruit collection.
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  • 文章类型: Journal Article
    病毒性疾病由于其快速传播和广泛影响而构成了严重的全球健康威胁。RNA依赖性RNA聚合酶(RdRp)参与合成,转录,以及病毒RNA在宿主中的复制。目前的研究调查了次级代谢物的抗病毒潜力,特别是那些来自细菌,真菌,和植物开发新药。使用结合分子对接和分子动力学(MD)模拟的虚拟筛选方法,我们旨在发现与五种不同逆转录病毒的RdRp具有强相互作用的化合物。根据每个病毒RdRp的对接得分,选择前五个化合物,绑定模式,分子相互作用,和药物相似特性。分子对接研究发现了几种具有抗RdRp抗病毒活性的代谢物。例如,细胞松弛素Z8对SARS-CoV-2的RdRp的对接得分最低,为-8.9(kcal/mol),对HIV-1的阿苏维酮D(-9.2kcal/mol),talaromyolideD(-9.9kcal/mol)丙型肝炎,针对埃博拉病毒和talaromyolideD的乙酰维酮D(-9.9kcal/mol)也保持了对登革病毒RdRp酶的最低对接评分-9.2kcal/mol。这些化合物显示出与批准靶向RdRp的标准药物(remdesivir-7.4kcal/mol)相当的显着抗病毒潜力,并且没有明显的毒性。分子动力学模拟证实,最佳选择的配体牢固地结合到它们各自的靶蛋白上,模拟时间为200ns。确定的先导化合物具有独特的药理学特征,使它们成为抗SARS-CoV-2抗病毒药物的潜在候选者。建议进一步的实验评估和调查以确定其功效和潜力。
    Viral diseases pose a serious global health threat due to their rapid transmission and widespread impact. The RNA-dependent RNA polymerase (RdRp) participates in the synthesis, transcription, and replication of viral RNA in host. The current study investigates the antiviral potential of secondary metabolites particularly those derived from bacteria, fungi, and plants to develop novel medicines. Using a virtual screening approach that combines molecular docking and molecular dynamics (MD) simulations, we aimed to discover compounds with strong interactions with RdRp of five different retroviruses. The top five compounds were selected for each viral RdRp based on their docking scores, binding patterns, molecular interactions, and drug-likeness properties. The molecular docking study uncovered several metabolites with antiviral activity against RdRp. For instance, cytochalasin Z8 had the lowest docking score of -8.9 (kcal/mol) against RdRp of SARS-CoV-2, aspulvinone D (-9.2 kcal/mol) against HIV-1, talaromyolide D (-9.9 kcal/mol) for hepatitis C, aspulvinone D (-9.9 kcal/mol) against Ebola and talaromyolide D also maintained the lowest docking score of -9.2 kcal/mol against RdRp enzyme of dengue virus. These compounds showed remarkable antiviral potential comparable to standard drug (remdesivir -7.4 kcal/mol) approved to target RdRp and possess no significant toxicity. The molecular dynamics simulation confirmed that the best selected ligands were firmly bound to their respective target proteins for a simulation time of 200 ns. The identified lead compounds possess distinctive pharmacological characteristics, making them potential candidates for repurposing as antiviral drugs against SARS-CoV-2. Further experimental evaluation and investigation are recommended to ascertain their efficacy and potential.
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