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Kinetic control of nervous necrosis virus by cell-derived antiviral substance and metabolic state in fish cell lines 细胞源性抗病毒物质对神经坏死病毒的动力学控制及鱼细胞系代谢状态

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-12-02 DOI: 10.1016/j.virol.2025.110767

Han Sol Lee , Toyohiko Nishizawa

Nervous necrosis virus (NNV) causes high mortality in many fish species. We previously reported that sevenband grouper fin (SeGF) cells persistently infected with NNV (PI-SeGF^NNV) produce a small-molecule, antiviral substance that suppresses NNV multiplication and cellular metabolic activity. In this study, we investigate the kinetics of NNV multiplication, cellular metabolic rate and production of antiviral substance in striped snakehead (SSN-1), SeGF and PI-SeGF^NNV cells at culture temperatures of 17–32 °C. Our results demonstrated that the NNV multiplication rate reached a maximum of 2.0 log₁₀ fold/day and was more closely associated with cellular metabolic rate rather than culture temperature. In SeGF and PI-SeGF^NNV cells, antiviral substance production increased with rising metabolic activity, and its accumulation, in turn, suppressed both cellular growth and viral multiplication. Notably, when the NNV multiplication rate was suppressed to <1.5 log₁₀ fold/day in SeGF cells, the maximum viral titer remained below 10^7.5 TCID₅₀/ml. In contrast, when the antiviral response was insufficient, the viral titer increased to ≥ 10^9.0 TCID₅₀/ml. SSN-1 cells cultured at < 28 °C produced little to no antiviral substance, resulting in consistently high viral yields regardless of culture temperature. These findings suggest that the kinetics of NNV multiplication are controlled by the balance between production of antiviral substance and cellular metabolic rate rather than temperature alone. This mechanistic insight may help explain how low-temperature exposure or persistent infection can control the multiplication of viruses in fish and devise strategies to combat viral infections in the aquaculture industry.

神经坏死病毒（NNV）在许多鱼类中引起高死亡率。我们之前报道了持续感染NNV的七波段石斑鱼鳍（SeGF）细胞（PI-SeGFNNV）产生一种小分子抗病毒物质，抑制NNV增殖和细胞代谢活性。在本研究中，我们研究了在17-32℃的培养温度下，条纹蛇头（SSN-1）、SeGF和PI-SeGFNNV细胞NNV的增殖动力学、细胞代谢率和抗病毒物质的产生。结果表明，NNV增殖率最高可达2.0 log10倍/天，与细胞代谢率而非培养温度的关系更密切。在SeGF和PI-SeGFNNV细胞中，抗病毒物质的产生随着代谢活性的升高而增加，其积累反过来抑制细胞生长和病毒增殖。值得注意的是，在SeGF细胞中，当NNV增殖率被抑制到1.5 log10倍/天时，最大病毒滴度保持在107.5 TCID50/ml以下。相反，当抗病毒反应不足时，病毒滴度升高至≥109.0 TCID50/ml。在28°C下培养的SSN-1细胞几乎不产生抗病毒物质，无论培养温度如何，病毒产量始终很高。这些发现表明，NNV增殖的动力学是由抗病毒物质的产生和细胞代谢率之间的平衡控制的，而不仅仅是温度。这种机制的见解可能有助于解释低温暴露或持续感染如何控制鱼体内病毒的繁殖，并制定对抗水产养殖业病毒感染的策略。

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引用次数: 0

Genomic characterization of the Vibrio parahaemolyticus strain CIBGEN003 and mid-stage RNA-Seq analysis during phage vB_Vp_PvVp04_M infection 副溶血性弧菌CIBGEN003的基因组特征及噬菌体vB_Vp_PvVp04_M感染中期RNA-Seq分析

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-12-02 DOI: 10.1016/j.virol.2025.110769

Irais Ramírez-Sánchez, Alberto Peña-Rodríguez, Cristina Escobedo-Fregoso, Martín Ramírez-Orozco, Alexis Sebastián Martínez-López, Diana R. Barajas-Sandoval, Eduardo Quiroz-Guzmán

Vibrio parahaemolyticus is a primary etiological agent of acute hepatopancreatic necrosis disease (AHPND), which has caused substantial economic losses in the global aquaculture systems. Nowadays, antimicrobial resistance is a significant problem that makes producers search for alternative treatments to eradicate these infections; phages are an excellent strategy to address this issue. This study reported the genomic characterization of V. parahaemolyticus strain identified as V. parahaemolyticus CIBGEN003, isolated from a shrimp farm. We tested this strain against a Vibrio phage, to identify the genes involved in the infection of the phage vB_PvVP04_M in V. parahaemolyticus CIBGEN003 at 10 min after phage infection and before the lysis process. Phage genes transcribed at 10 min were associated to nucleotide metabolism and gene expression regulation; however, the expression of genes involved in virion structure and lysis remained unchanged. In addition, 22 bacterial genes were differentially transcribed at this time point, where upregulated genes are involved in cellular processes, including electron transfer and protein folding. In contrast downregulated genes were associated with nitrate assimilation and oxidative stress. This approach provided a better understanding of the transcriptional response to the bacterial-phage interaction before bacterial lysis.

副溶血性弧菌是急性肝胰腺坏死病（AHPND）的主要病原，在全球水产养殖系统中造成了巨大的经济损失。如今，抗微生物药物耐药性是一个重大问题，促使生产者寻找替代治疗方法来根除这些感染；噬菌体是解决这一问题的绝佳策略。本研究报道了从某对虾养殖场分离的副溶血性弧菌CIBGEN003的基因组特征。在噬菌体感染后10分钟和裂解前，我们对该菌株进行了噬菌体vB_PvVP04_M感染副溶血性弧菌CIBGEN003的基因鉴定。10 min转录的噬菌体基因与核苷酸代谢和基因表达调控有关；然而，参与病毒粒子结构和裂解的基因的表达保持不变。此外，22个细菌基因在这个时间点被差异转录，其中上调的基因参与细胞过程，包括电子转移和蛋白质折叠。相反，下调基因与硝酸盐同化和氧化应激相关。这种方法提供了更好的理解在细菌裂解前细菌-噬菌体相互作用的转录反应。

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引用次数: 0

Attenuation of a contemporary Chinese PRRSV-1 strain via serial cell passage and evaluation of its protective efficacy as a modified live virus vaccine candidate 当代中国一株PRRSV-1的细胞连续传代衰减及其作为修饰活病毒候选疫苗的保护效果评价

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-29 DOI: 10.1016/j.virol.2025.110746

Jianming Long , Keyi Liu , Yiting Chen , Xindong Wang , Zhiying Su , Guoyang Li , Kang Zhang , Tongwei Ren , Yifeng Qin , Kang Ouyang , Ying Chen , Weijian Huang , Yeshi Yin , Yingyi Wei , Zuzhang Wei

Porcine Reproductive and Respiratory Syndrome Virus type 1 (PRRSV-1) imposes substantial economic burdens on global swine production. In China, where only subtype 1 strains circulate across 23 provinces, evolving subpopulations challenge existing control measures. The absence of licensed PRRSV-1 vaccines in China underscores the urgency of developing tailored vaccine candidates against circulating strains. This study attenuated a contemporary Chinese PRRSV-1 isolate (GXFS20220129) through 100 serial passages (P100) on MARC-145 cells and evaluated its efficacy as a modified live virus (MLV) candidate. In vitro characterization revealed enhanced growth kinetics and increased plaque morphology in P100. Whole-genome sequencing identified 37 nucleotide mutations and 19 amino acid substitutions in P100, concentrated in the nsp1-3 and GP2 regions, potentially associated with attenuation. Immunogenicity and protection were assessed in piglets. The P100-immunized group exhibited no clinical signs post-challenge, maintained weight gain equivalent to blank controls, and demonstrated robust seroconversion by 14 dpi. The area under the curve (AUC) analyses (28–42 dpi) showed significantly lower nasal-shedding and higher antibody responses in vaccinated pigs, whereas cumulative viremia and rectal-shedding AUCs were not significantly different between challenged groups. Vaccination attenuated viremia, accelerated viral clearance, significantly reduced viral loads in systemic tissues (heart, liver, lung, kidney) and intestinal segments (duodenum, ileum, rectum), and altered shedding kinetics. Gross and histopathological lesions in lungs and intestines were substantially mitigated in immunized animals. Collectively, serial passage generated an attenuated PRRSV-1 strain conferring comprehensive protection against homologous challenge, supporting its potential as an MLV candidate for PRRSV-1 control in China.

猪繁殖与呼吸综合征病毒1型（PRRSV-1）给全球生猪生产带来了巨大的经济负担。在中国，只有1型毒株在23个省份传播，不断演变的亚群对现有的控制措施构成挑战。中国缺乏获得许可的PRRSV-1疫苗，这凸显了开发针对流行毒株的定制候选疫苗的紧迫性。本研究通过100次连续传代（P100）对中国当代PRRSV-1分离物GXFS20220129在MARC-145细胞上进行减毒，并评估其作为修饰活病毒（MLV）候选物的效力。体外表征显示P100的生长动力学增强，斑块形态增加。全基因组测序鉴定出P100中37个核苷酸突变和19个氨基酸替换，集中在nsp1-3和GP2区域，可能与衰减有关。对仔猪进行免疫原性和保护性评价。p100免疫组在攻击后没有表现出任何临床症状，保持与空白对照组相当的体重增加，并表现出14 dpi的强劲血清转化。曲线下面积（AUC）分析（28-42 dpi）显示，接种猪的鼻脱落显著降低，抗体反应显著提高，而累积病毒血症和直肠脱落AUC在攻毒组之间无显著差异。疫苗可减轻病毒血症，加速病毒清除，显著降低全身组织（心、肝、肺、肾）和肠段（十二指肠、回肠、直肠）的病毒载量，并改变脱落动力学。免疫动物肺和肠的大体和组织病理学病变明显减轻。总的来说，序列传代产生了一个减毒的PRRSV-1菌株，对同源攻击具有全面的保护作用，支持其作为中国PRRSV-1控制的MLV候选株的潜力。

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引用次数: 0

Decoding the metabolic crosstalk between glycolysis and RNA viral pathogenesis 解码糖酵解与RNA病毒发病机制之间的代谢串扰

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-29 DOI: 10.1016/j.virol.2025.110766

Vijay Singh Bohara, Sachin Kumar

RNA viruses induce metabolic reprogramming in the host cells by shifting metabolism towards enhanced glycolysis, rapidly converting glucose to lactate, a phenomenon known as the Warburg effect. This metabolic shift supports viral replication by providing essential macromolecular precursors and energy. They regulate key components of glycolysis, including glucose transporters and glycolytic enzymes, to facilitate increased glucose uptake and its flux. Glycolysis is also crucial for the activation of immune cells and the regulation of cytokine production. This review summarises the molecular mechanisms driving these metabolic alterations to better understand the virus-host interactions. The factors regulating these mechanisms can be potential therapeutic targets for controlling viral infections.

RNA病毒通过将代谢转向增强的糖酵解，迅速将葡萄糖转化为乳酸，从而在宿主细胞中诱导代谢重编程，这种现象被称为Warburg效应。这种代谢转变通过提供必需的大分子前体和能量来支持病毒复制。它们调节糖酵解的关键成分，包括葡萄糖转运体和糖酵解酶，以促进葡萄糖的摄取和通量的增加。糖酵解对于激活免疫细胞和调节细胞因子的产生也至关重要。本文综述了驱动这些代谢变化的分子机制，以更好地了解病毒与宿主的相互作用。调节这些机制的因子可能是控制病毒感染的潜在治疗靶点。

引用次数: 0

Immunogenicity and efficacy of commercial poultry avian influenza vaccines against HPAI A(H5N1) clade 2.3.4.4b viruses in Mexico 墨西哥市售家禽禽流感疫苗对HPAI A（H5N1）分支2.3.4.4b病毒的免疫原性和效力

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-29 DOI: 10.1016/j.virol.2025.110765

David C. Brice , Konstantin Andreev , Lance Miller , Christopher Patton , Patrick Seiler , Tehui Garcia , Morgan L. LeBlanc , Taylor Hibler , Eda Ozdemir , Alexandra H. Mandarano , Faten Okda , Alejandro García , Richard J. Webby , Ahmed Kandeil

The high-pathogenicity avian influenza A (H5N1) viruses of clade 2.3.4.4 b have been detected in domestic poultry and wild birds in Mexico. Vaccination with H5 vaccines has been implemented as a complementary influenza control strategy in poultry in many countries, including Mexico. Continuous reevaluation of the efficacy of licensed vaccines against emerging viruses is required to ensure adequate control of virus transmission and infection. Some commercial poultry H5 vaccines used in Mexico are produced from vaccine seed viruses that are genetically distinct from clade 2.3.4.4 b viruses. Here, we studied the efficacy of four commercial H5 poultry vaccines widely used in the Mexican market and an experimental inactivated, adjuvanted vaccine against a recent North American high-pathogenicity avian influenza A (H5N1) 2.3.4.4 b virus. Chickens in all vaccinated groups developed antibodies to the viral nucleoprotein as detected by enzyme-linked immunosorbent assay. Although some of the commercial vaccines did not elicit detectable hemagglutination inhibition or microneutralization titers, all vaccines provided 80 %–100 % protection from mortality. Immunophenotyping of the peripheral blood mononuclear cells of vaccinated chickens showed that these vaccines did not elicit peripheral T-cell or other non-B cell responses that could explain the observed protection. Accordingly, we recommend continued evaluation of vaccine efficacy against evolving viruses and further efforts to identify non-neutralizing antibody correlates of protection.

在墨西哥的家禽和野禽中发现了2.3.4.4 b进化支的高致病性H5N1型禽流感病毒。在包括墨西哥在内的许多国家，已在家禽中实施H5疫苗接种，作为一项补充性流感控制战略。为确保充分控制病毒传播和感染，需要不断重新评估获得许可的疫苗对新出现病毒的效力。墨西哥使用的一些商业家禽H5疫苗是由疫苗种子病毒生产的，这些病毒在基因上与2.3.4.4 b进化支病毒不同。在这里，我们研究了墨西哥市场上广泛使用的四种商用H5家禽疫苗和一种实验性灭活佐剂疫苗对最近出现的北美高致病性禽流感a (H5N1) 2.3.4.4 b病毒的有效性。经酶联免疫吸附试验检测，所有接种组的鸡均产生病毒核蛋白抗体。虽然一些商业疫苗没有引起可检测的血凝抑制或微中和滴度，但所有疫苗都提供80% - 100%的死亡率保护。接种疫苗的鸡的外周血单核细胞的免疫表型显示，这些疫苗不会引起外周t细胞或其他非b细胞反应，这可以解释观察到的保护作用。因此，我们建议继续评估疫苗对不断演变的病毒的效力，并进一步努力确定与保护作用相关的非中和抗体。

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引用次数: 0

The roles of sugar metabolism mechanisms and metabolites in viral infections 糖代谢机制和代谢物在病毒感染中的作用。

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-28 DOI: 10.1016/j.virol.2025.110764

Jieyi He , Xianghong Ju , A.M. Abd El-Aty , Xiaoxi Liu , Xiaowen Li

Viral infections pose a persistent challenge to global health by triggering sophisticated molecular interactions and extensive metabolic reprogramming within host organisms. Glycolysis—a central energy metabolism pathway—is dynamically and bidirectionally regulated during infection, reflecting a continuous metabolic interplay between pathogen and host. Rather than maintaining a static metabolic state, glycolytic flux is shaped by competing demands: viruses actively stimulate glycolysis to support replication, while hosts suppress it as a defensive strategy. This regulatory balance shifts across distinct stages of infection—from viral entry and replication peaks to immune clearance—resulting in phase-specific fluctuations in glycolytic activity that reveal a dynamic metabolic tug-of-war. In this review, we synthesize current understanding of how viruses recurrently activate host glycolysis to enhance replication, detailing conserved mechanisms of metabolic hijacking and the multilayered counterstrategies employed by the host. We further evaluate emerging therapeutic approaches, including targeted glycolytic inhibitors and combined immunomodulatory regimens, while addressing challenges related to specificity and efficacy. Finally, we highlight promising research directions such as tissue-specific nanodelivery platforms and single-cell multi-omics integration, which together offer a conceptual framework for developing next-generation antiviral therapies.

病毒感染通过触发宿主体内复杂的分子相互作用和广泛的代谢重编程，对全球健康构成了持续的挑战。糖酵解是一种核心的能量代谢途径，在感染过程中受到动态和双向调节，反映了病原体和宿主之间持续的代谢相互作用。糖酵解通量不是维持静态代谢状态，而是由相互竞争的需求形成：病毒积极刺激糖酵解以支持复制，而宿主则将其抑制为防御策略。这种调节平衡在感染的不同阶段发生变化——从病毒进入和复制高峰到免疫清除——导致糖酵解活性的阶段特异性波动，揭示了一种动态的代谢拉锯战。在这篇综述中，我们综合了目前对病毒如何反复激活宿主糖酵解以增强复制的理解，详细介绍了代谢劫持的保守机制和宿主采用的多层对抗策略。我们进一步评估新兴的治疗方法，包括靶向糖酵解抑制剂和联合免疫调节方案，同时解决与特异性和有效性相关的挑战。最后，我们强调了有前景的研究方向，如组织特异性纳米递送平台和单细胞多组学整合，它们共同为开发下一代抗病毒疗法提供了概念框架。

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引用次数: 0

Characterization of the antibody diversity of glycoprotein E2 domain B/C in pestivirus by using high-throughput single B cell technology 利用高通量单B细胞技术鉴定鼠疫病毒糖蛋白E2结构域B/C的抗体多样性。

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-27 DOI: 10.1016/j.virol.2025.110762

Huanhuan Liu , Chao Tong , Zhi Sun , Pengju Guo , Ning Chen , Jue Liu

Microfluidic technology is an advanced platform for isolating single B cells and constructing paired antibody chain libraries. In the present study, a customized immunization approach coupled with a high-throughput, microfluidic-based single B cell platform was utilized to identify and characterize a pool of monoclonal antibodies (mAbs) targeting the B/C domain of the classical swine fever virus (CSFV) E2 protein. A total of 4241 antigen-specific plasma cells were isolated and subsequently subjected to next-generation sequencing, which yielded 82 distinct naturally paired antibody sequences. Binding assays performed on 81 mAbs revealed that 38 mAbs effectively bound to the B/C domain of the CSFV QZ07 strain E2 protein. Among these, 14 mAbs specifically recognized the B/C domain of genotype 2 QZ07-E2, and 24 mAbs reacted with both genotype 2 QZ07-E2 and genotype 1 C-E2; within the latter group, 8 mAbs exhibited cross-reactivity with the B/C domain of other pestiviruses. Phylogenetic profiling of CDR sequences also classified these antibodies into three distinct clusters, which showed a strong correlation with binding profiles. These findings suggest the presence of novel, broadly reactive pan-pestivirus epitopes in the B/C domain. The integration of microfluidics with high-throughput sequencing in single B cell technology in this study not only accelerates the antibody discovery process but also provides a robust platform to investigate the antigenicity of key pathogen proteins for developing diagnostic assays and next-generation marker vaccines.

微流控技术是分离单个B细胞和构建配对抗体链文库的先进平台。在本研究中，利用定制免疫方法结合高通量、基于微流体的单B细胞平台，鉴定和表征了针对猪瘟病毒（CSFV） E2蛋白B/C结构域的单克隆抗体池。共分离出4241个抗原特异性浆细胞，随后进行下一代测序，得到82个不同的自然配对抗体序列。对81个单克隆抗体进行的结合实验显示，38个单克隆抗体能有效结合猪瘟病毒QZ07株E2蛋白的B/C结构域。其中，14单抗特异性识别基因2型QZ07-E2的B/C结构域，24单抗与基因2型QZ07-E2和基因1型C- e2均有反应；后一组中有8个单抗与其他鼠疫病毒的B/C结构域具有交叉反应性。CDR序列的系统发育分析也将这些抗体分为三个不同的簇，这与结合谱有很强的相关性。这些发现提示在B/C结构域中存在新的、广泛反应的泛鼠疫病毒表位。本研究将微流体技术与高通量单B细胞测序技术相结合，不仅加快了抗体的发现过程，而且为研究关键病原体蛋白的抗原性提供了一个强大的平台，可用于开发诊断分析和下一代标记疫苗。

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引用次数: 0

Genomic diversity and reassortment of highly pathogenic avian influenza A/H5N1 virus (clade 2.3.4.4b) in Brazil: Evidence of multiple introductions and intra-epidemic reassortment in 2025 巴西高致病性禽流感A/H5N1病毒（进化支2.3.4.4b）的基因组多样性和重配：2025年多次引入和流行内重配的证据

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-27 DOI: 10.1016/j.virol.2025.110751

Anselmo Vasconcelos Rivetti Jr. , Dilmara Reischak , Lorcan Carnegie , Juliana Nabuco Pereira Otaka , Christian Steffe Domingues , Fernanda Gomes Cardoso , Ana Luiza Savioli da Silva , Soraya Cecília Albieri Camillo , Aristóteles Goés-Neto , Marcelo Fernandes Camargos

Highly pathogenic avian influenza (HPAI) A/H5N1, clade 2.3.4.4b, has spread globally, with the first outbreak in a commercial poultry farm in Brazil reported in 2025. This study aimed to genetically characterize A/H5N1 samples from multiple Brazilian regions using whole-genome next-generation sequencing (NGS) to investigate viral diversity and reassortment events. Phylogenetic analyses revealed that Brazilian isolates segregated into two distinct clades: one showing high similarity to viruses detected in Argentina in 2025 suggesting adaptation of new reassortants along a regional dissemination route in South America; and another clustering with North American isolates, indicating an independent introduction. Genotyping confirmed the emergence of previously unreported genomic rearrangements in South America, underscoring the complexity of viral evolution in the region. These findings highlight intra-epidemic genomic diversity and reinforce the need for continuous, in-depth molecular surveillance to monitor the dynamics and potential impacts of A/H5N1 on animal and public health.

高致病性禽流感（HPAI） A/H5N1，分支2.3.4.4b，已在全球蔓延，2025年在巴西的一个商业家禽养殖场报告了首次暴发。本研究旨在利用全基因组新一代测序（NGS）对来自巴西多个地区的A/H5N1样本进行遗传表征，以调查病毒多样性和重组事件。系统发育分析显示，巴西的分离株分离成两个不同的分支：一个与2025年在阿根廷发现的病毒高度相似，表明在南美洲的区域传播路线上有新的重组适应；另一个与北美分离株聚类，表明是独立引进的。基因分型证实了南美洲出现了以前未报道的基因组重排，强调了该地区病毒进化的复杂性。这些发现突出了流行内基因组多样性，并强调需要进行持续深入的分子监测，以监测A/H5N1的动态和对动物和公共卫生的潜在影响。

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引用次数: 0

Dynamics of virus infection in a Wolbachia-infected host 沃尔巴克氏体感染宿主的病毒感染动力学

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-27 DOI: 10.1016/j.virol.2025.110759

Angelique K. Asselin, Jan Engelstädter, Karyn N. Johnson

Wolbachia is a bacterium that blocks viruses and protects its arthropod hosts from infection. Whilst Wolbachia blocking is used as a strategy to prevent mosquito-borne disease, the mechanisms of Wolbachia-mediated viral blocking are not well characterised. Several mechanisms have been implicated, but it is often unclear their contribution to the overall blocking and how broadly they apply across host-virus-Wolbachia systems. Wolbachia's impact on viral dynamics and pathogenicity in individual Drosophila hosts was measured to explore what Wolbachia-mediated changes dominate the blocking phenotype. The empirical data was combined with a dynamical model to look at the impact of a series of parameters. This model described changes through time to susceptible cells, infected cells, and free virion particles. Results showed that Wolbachia reduced the accumulation of viral RNA and infectious viruses. The maximum amount of viral RNA was lower in individuals with Wolbachia, while the maximum amount of infectious virus was the same. These viral dynamics of Wolbachia-infected individuals could be recapitulated with a lower rate of viral infection of susceptible cells, lower viral release, a smaller number of susceptible cells or smaller burst size or various combinations of these processes. Experimental testing of the importance of these processes may be required to resolve their contribution to Wolbachia-mediated virus blocking. As further empirical data is added, the dynamical modelling approach may help guide decisions on which large impact mechanisms to focus on for functional approaches.

沃尔巴克氏体是一种细菌，可以阻断病毒并保护其节肢动物宿主免受感染。虽然沃尔巴克氏体阻断被用作预防蚊媒疾病的一种策略，但沃尔巴克氏体介导的病毒阻断的机制尚未得到很好的表征。有几种机制已被涉及，但通常不清楚它们对整体阻断的贡献以及它们在宿主-病毒-沃尔巴克氏体系统中的应用范围。沃尔巴克氏体对单个果蝇宿主的病毒动力学和致病性的影响被测量，以探索沃尔巴克氏体介导的哪些变化主导了阻断表型。将经验数据与动态模型相结合，以观察一系列参数的影响。该模型描述了易感细胞、感染细胞和游离病毒粒子随时间的变化。结果表明沃尔巴克氏体减少了病毒RNA和感染性病毒的积累。沃尔巴克氏体个体病毒RNA的最大数量较低，而感染性病毒的最大数量相同。沃尔巴克氏体感染个体的这些病毒动力学可以概括为易感细胞的病毒感染率较低，病毒释放较低，易感细胞数量较少或爆发大小较小或这些过程的各种组合。可能需要对这些过程的重要性进行实验测试，以确定它们对沃尔巴克氏体介导的病毒阻断的贡献。随着进一步的经验数据的增加，动态建模方法可能有助于指导决策，哪些大的影响机制将重点放在功能方法上。

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引用次数: 0

Spumigins produced by Nodularia spumigena are natural serine protease inhibitors with anti-SARS-CoV-2 activity Spumigins是一种天然丝氨酸蛋白酶抑制剂，具有抗sars - cov -2活性

IF 2.4 3区医学 Q3 VIROLOGY

Virology

Pub Date : 2025-11-27 DOI: 10.1016/j.virol.2025.110763

Aleksandra Milewska , Robert Konkel , Markus Hoffmann , Stefan Pöhlmann , Artur Szczepański , Tony Fröhlich , Grzegorz Popowicz , Donata Overlinge , Hanna Mazur-Marzec , Krzysztof Pyrć

COVID-19, caused by SARS-CoV-2, has led to significant morbidity and mortality worldwide. The pandemic has sparked extensive efforts to develop therapeutic strategies targeting either the virus itself or human proteins involved in the infection, resulting in hundreds of potential drugs and numerous clinical trials. In the search for new anti-SARS-CoV-2 drug candidates, we focussed on natural products. Using the cyanobacteria as a source of new structures due to their unique metabolism, two spumigins were isolated from the Baltic cyanobacterium Nodularia spumigena and tested for their activity against SARS-CoV-2. These compounds efficiently reduced SARS-CoV-2 infection in human A549^ACE2/TMPRSS2 cells and fully differentiated primary human airway epithelium cell systems, in which viral entry depends on activation of the viral spike protein by the cellular serine protease, such as TMPRSS2. In contrast, the compounds did not inhibit viral replication in Vero cells, which lack TMPRSS2 but have high levels of cysteine protease cathepsin L, which may serve as an alternative for spike protein activation. Biochemical assays showed that spumigins inhibit TMPRSS2 with an EC₅₀ ranging from 17 to 85 nM at which no toxicity is observed. Good parameters of identified inhibitors prove that cyanobacteria may serve as a rich source for new scaffolds reaching beyond the canonical chemical combinatorial space.

由SARS-CoV-2引起的COVID-19在世界范围内导致了很高的发病率和死亡率。大流行引发了广泛的努力，以开发针对病毒本身或与感染有关的人类蛋白质的治疗策略，导致数百种潜在药物和无数临床试验。在寻找新的抗sars - cov -2候选药物时，我们将重点放在天然产物上。由于蓝藻具有独特的代谢功能，因此将其作为新结构的来源，从波罗的海蓝藻结核菌中分离出两种spumigins，并测试了它们对SARS-CoV-2的活性。这些化合物有效降低了SARS-CoV-2在人A549ACE2/TMPRSS2细胞中的感染，并完全分化了人气道上皮原代细胞系统，其中病毒的进入依赖于细胞丝氨酸蛋白酶（如TMPRSS2）对病毒刺突蛋白的激活。相比之下，这些化合物没有抑制病毒在缺乏TMPRSS2但具有高水平半胱氨酸蛋白酶组织蛋白酶L的Vero细胞中的复制，这可能是刺突蛋白激活的替代方法。生化实验表明，spumigins抑制TMPRSS2的EC50在17 ~ 85 nM范围内，无毒性。所鉴定的抑制剂的良好参数证明蓝藻可能作为超越规范化学组合空间的新支架的丰富来源。

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引用次数: 0