Nipah Virus

尼帕病毒
  • 文章类型: Journal Article
    亨尼帕病毒,高度致命的人畜共患病毒,死亡率高达100%,对人类构成重大威胁。尽管有零星的病例,包括雪松的感染,朗亚,和尼帕病毒,没有确定的治疗药物或疫苗。缺乏特定的药物使我们从印度药用植物中探索了57种无毒化合物,从232种化合物中选择,旨在对抗这些病毒。通过计算机模拟ADMET分析,三个化合物-穿心莲内酯,翼状精蛋白和红景天苷因其特殊的无毒特性而脱颖而出。这些化合物进行了硅目标预测,与雪松的分子对接和动力学,朗亚,和来自蛋白质数据库的尼帕病毒蛋白质。其中,穿心莲内酯在雪松病毒附着G蛋白结合袋中显示出最有希望的负自由能得分和稳定性。在整个模拟过程中,翼精蛋白和红景天苷对Langya和Nipah病毒靶蛋白均具有功效。这些化合物不仅表现出抗病毒特性,而且还表现出免疫调节,抗炎,和我们的计算机研究对肝脏的保护作用。它们作为治疗或预防性措施的潜力使它们成为进一步研究和开发的有希望的候选人。
    在线版本包含补充材料,可在10.1007/s40203-024-00236-x获得。
    Henipaviruses, highly fatal zoonotic viruses with mortality rates up to 100%, pose a significant threat to humans. Despite sporadic cases, including infections from Cedar, Langya, and Nipah Viruses, there are no established drugs or vaccines for treatment. This lack of specific medication led us to explore 57 non-toxic compounds from Indian Medicinal Plants, selected from 232 compounds, aiming to combat these viruses. Through in silico ADMET analyses, Three compounds-andrographolide, pterygospermin and Salidroside-stood out for their exceptional non-toxic properties. These compounds underwent in silico target prediction, molecular docking and dynamics with Cedar, Langya, and Nipah Virus proteins from the Protein Data Bank. Among them, Andrographolide displayed the most promising negative free energy scores and stability in Cedar Virus-Attachment G-Protein binding pockets. Pterygospermin and Salidroside showed efficacy against Langya and Nipah Virus target proteins throughout the simulation. These compounds not only exhibited antiviral properties but also demonstrated immunomodulatory, anti-inflammatory, and hepatoprotective effects by our in-silico studies. Their potential as treatments or preventive measures against henipaviral infections makes them promising candidates for further research and development.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00236-x.
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  • 文章类型: Journal Article
    尼帕病毒,一种来自副粘病毒科的人畜共患病毒已经导致了大量的生命损失,直到印度最近一次在喀拉拉邦爆发。该病毒具有相当高的死亡率以及缺乏特征性症状,这导致病毒检测的延迟。尽管已发现单克隆抗体治疗与favipiravir一起有效,但尚无针对该病毒的特异性疫苗。该病毒引起的高死亡率和并发症强调了开发替代疫苗接种模式的必要性。在本研究中设计了一种这样的方法,使用由免疫学上重要的表位组成的肽混合物用作疫苗。分析了用于该研究的人类白细胞抗原在各种印度族裔中的存在。这项研究可能会作为一个新的途径,为开发更有效的肽鸡尾酒疫苗在最近的未来基于人口遗传学和种族。
    Nipah virus, a zoonotic virus from the family Paramyxoviridae has led to significant loss of lives till date with the most recent outbreak in India reported in Kerala. The virus has a considerably high mortality rate along with lack of characteristic symptoms which results in the delay of the virus detection. No specific vaccine is available for the virus although monoclonal antibody treatment has been seen to be effective along with favipiravir. The high mortality and complications caused by the virus underscores the necessity to develop alternative modes of vaccination. One such method has been designed in this study using peptide cocktail consisting of the immunologically important epitopes for use as vaccine. The human leucocytic antigens that are used for the study were analyzed for their presence in various ethnic Indian populations. This study may serve as a new avenue for development of more efficient peptide cocktail vaccines in recent future based on the population genetics and ethnicity.
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  • 文章类型: Journal Article
    当前的研究试图通过计算机分子对接研究评估53种天然化合物作为尼帕病毒附着糖蛋白(NiVG)抑制剂的潜力。四(4)种选定化合物(柚皮苷,MulberrofuryB,芦丁和槲皮素3-半乳糖苷)通过主成分分析(PCA)揭示了常见的药效团,即四个H键受体,一个H键供体和两个芳香基团负责与靶蛋白的残余相互作用。在这四种化合物中,发现柚皮苷对靶蛋白NiVG具有最高的抑制潜力(-9.19kcalmol-1),与对照药物相比,利巴韦林(-6.95kcalmol-1)。分子动力学模拟表明,柚皮苷在接近天然的生理条件下可以与靶蛋白形成稳定的复合物。最后,MM-PBSA(分子力学-泊松-玻尔兹曼溶剂-可接近表面积)分析与我们的分子对接结果一致,结果表明,柚皮苷(-218.664kJmol-1)比对照药物利巴韦林(-83.812kJmol-1)能与靶蛋白NiVG强结合。
    在线版本包含补充材料,可在10.1007/s13205-023-03595-y获得。
    The current study attempted to evaluate the potential of fifty-three (53) natural compounds as Nipah virus attachment glycoprotein (NiV G) inhibitors through in silico molecular docking study. Pharmacophore alignment of the four (4) selected compounds (Naringin, Mulberrofuran B, Rutin and Quercetin 3-galactoside) through Principal Component Analysis (PCA) revealed that common pharmacophores, namely four H bond acceptors, one H bond donor and two aromatic groups were responsible for the residual interaction with the target protein. Out of these four compounds, Naringin was found to have the highest inhibitory potential ( - 9.19 kcal mol-1) against the target protein NiV G, when compared to the control drug, Ribavirin ( - 6.95 kcal mol-1). The molecular dynamic simulation revealed that Naringin could make a stable complex with the target protein in the near-native physiological condition. Finally, MM-PBSA (Molecular Mechanics-Poisson-Boltzmann Solvent-Accessible Surface Area) analysis in agreement with our molecular docking result, showed that Naringin ( - 218.664 kJ mol-1) could strongly bind with the target protein NiV G than the control drug Ribavirin ( - 83.812 kJ mol-1).
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13205-023-03595-y.
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  • 文章类型: Journal Article
    科学界继续对基于RNA的具有巨大功效的疫苗印象深刻,快速合成和快速上市。传统疫苗可能需要大剂量或重复注射以实现针对病毒的保护表达;自扩增mRNA疫苗解决了这一限制。因此,对尼帕病毒的最抗原成分进行了彻底的检查,以设计抗原的编码序列,这将引发病毒特异性免疫反应。之后,我们预测并评估了NiVG蛋白的表位。我们雇佣了8个HTL,2个CTL和3个B细胞表位。通过在HLA等位基因和表位之间进行对接来进行结构相容性研究,以了解表位的免疫反应。使用接头连接抗原的整个肽编码序列以设计疫苗的结构。使用protparam服务器评估设计的疫苗构建体的物理化学参数。稍后,将疫苗序列转化为cDNA。我们在编码序列的起始处插入了表达基因的复制酶以进行自我扩增。接下来,为了制定最终版本的疫苗信号序列被添加。基于这些发现,这种mRNA疫苗似乎是对抗尼帕病毒的一种有希望的选择.由RamaswamyH.Sarma沟通。
    The scientific community continues to be impressed with RNA-based vaccines with great efficacy, quick synthesis and speed-to-market. The traditional vaccine may require large doses or repeat injections to achieve an expression for protection against the virus; the self-amplifying mRNA vaccine addresses this limitation. Therefore, a thorough examination of the most antigenic component of the Nipah virus was carried out to design the coding sequence of an antigen, which will provoke a virus-specific immune response. After that, we predicted and evaluated epitopes from NiV G-protein. We employed 8 HTL, 2 CTL and 3 B-cell epitopes. The study of structural compatibility was done by performing docking between HLA alleles and epitopes to get insights into the immune response of epitopes. The entire peptide coding sequence of an antigen was linked using a linker to design the structure of the vaccine. Physicochemical parameters of the designed vaccine constructs were assessed using a protparam server. Later, the vaccine sequence was converted into cDNA. We inserted a gene-expressing replicase at the start of a coding sequence for self-amplification. Next, to formulate the final version of vaccine signal sequences were added. Based on these findings, this mRNA vaccine appears to be a promising option against the Nipah virus.Communicated by Ramaswamy H. Sarma.
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  • 文章类型: Journal Article
    Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.
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  • 文章类型: Journal Article
    BACKGROUND: An outbreak of Nipah virus infection was confirmed in Kerala, India in May 2018. Five out of 23 cases including the first laboratory-confirmed case were treated at Baby Memorial Hospital (BMH), Kozhikode. The study describes the clinical characteristics and epidemiology of the Nipah virus outbreak at Kozhikode during May 2018.
    OBJECTIVE: To study the clinical and epidemiological profile of Nipah virus epidemic that occurred in Kerala in May 2018.
    METHODS: A collaborative team of physicians and epidemiologists from BMH, Medical College Hospital (MCH) Kozhikode and from the Indian Medical Association (IMA) conducted this study. The clinical and exposure history and the data on outbreak response were gathered from hospital medical records and through interviewing patient relatives and health workers using questionnaires.
    RESULTS: It was identified that out of the 23 patients with Nipah virus infection, 21 (91.3%) expired. Out of the 21 patients, 18 tested positive for Nipah virus by Real Time polymerase chain reaction (RT-PCR). It has been found that only the index case was infected in the community from fruit bats. Rest of the cases were due to transmission of the virus at three public hospitals. Median age was 45 years. 65% of them were males. Median incubation period was 9.5 days. Fever (100%), altered sensorium (84.2%), tachycardia (63.1%), hypertension (36.8%), segmental myoclonus (15.7%), segmental sweating (15.7%) and shortness of breath (73.6%) were common features. Mean duration of illness was 6.4 days.
    CONCLUSIONS: The rapid spread of infection uncovered the miserable state of health care system in implementing infection control measures. The case fatality and the socio-economic burden warrant developing appropriate treatments, vaccines and diagnostics.
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  • 文章类型: Journal Article
    接触模式在疾病传播中起关键作用,疾病过程中接触的变化会影响传播,特别是伴随着宿主传染性的变化。我们对孟加拉国94例尼帕病毒病例患者的1642名接触者进行了调查,以确定随着疾病严重程度的发展,接触方式(身体和体液)如何变化。接触的数量随着严重程度的增加而增加,对于死亡的病例患者,在死亡之日达到顶峰。鉴于仅在尼帕病毒感染的致命病例中观察到传播,我们的研究结果表明,患病期间接触方式的变化会增加感染风险.
    Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1642 contacts of 94 Nipah virus case patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case patients who died, peaked on the day of death. Given transmission has only been observed among fatal cases of Nipah virus infection, our findings suggest that changes in contact patterns during illness contribute to risk of infection.
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  • 文章类型: Journal Article
    OBJECTIVE: Farms that are neighboring wildlife sanctuaries are at risk of spillover infection from wildlife, and the objective of this research is to examine the species diversity of Malaysian fruit bats in livestock farm in determining the possible risk of spill over infection to livestock.
    METHODS: Fifty individual fruit bats were captured using six mists net, from May to July 2017. The nets were set at dusk (1830 h) as bats emerge for foraging and monitored at every 30-min intervals throughout the night until dawn when they returned to the roost. The nets were closed for the day until next night, and captured bats were identified to species levels.
    RESULTS: All the captured bats were mega chiropterans, and Cynopterus brachyotis was the highest captured species, representing 40% of the total capture. Shannon-Weiner index is 2.80, and Simpson index is 0.2. Our result suggests that there is a degree of species dominance with low diversity in Lenggong Livestock Breeding Center.
    CONCLUSIONS: We concluded that fruit bats are indeed, encroaching livestock areas and the species identified could be a potential source of infection to susceptible livestock. Hence, an active surveillance should be embarked on farms that border wildlife sanctuaries.
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  • 文章类型: Comparative Study
    人类尼帕病毒(NiV)感染,在孟加拉国经常致命,主要是通过饮用被翼龙蝙蝠污染的原始椰枣汁传播的。我们评估了行为改变沟通干预对减少潜在的NiV污染的原始树液消耗的影响。在2012-2014年的树液收获季节,我们在两个领域实施了干预措施,并将结果与对照组进行了比较.在一个领域,我们传播了一条“不要喝生汁液”的信息,在另一个地区,鼓励只喝树液,如果它已经被保护免受蝙蝠污染的屏障(“只有安全的树液”)。干预后,与对照组相比,在两个干预领域中,有40%的受访者表示知道通过食用原始汁液而感染的疾病。报告的所有地区的原始树液消费量均下降。与对照组相比,干预区域的减少幅度并不明显。与没有暴露的受访者相比,直接暴露于“唯一安全的SAP”消息的受访者更有可能报告消耗来自受保护来源的原始SAP(25与15%,OR2.0,95%CI1.5-2.6,P<0.001)。虽然干预措施增加了两个干预领域的知识,“唯一安全的汁液”干预措施减少了对可能受NiV污染的汁液的暴露,应考虑将来传播。
    Human Nipah virus (NiV) infection, often fatal in Bangladesh, is primarily transmitted by drinking raw date palm sap contaminated by Pteropus bats. We assessed the impact of a behavior change communication intervention on reducing consumption of potentially NiV-contaminated raw sap. During the 2012-2014 sap harvesting seasons, we implemented interventions in two areas and compared results with a control area. In one area, we disseminated a \"do not drink raw sap\" message and, in the other area, encouraged only drinking sap if it had been protected from bat contamination by a barrier (\"only safe sap\"). Post-intervention, 40% more respondents in both intervention areas reported knowing about a disease contracted through raw sap consumption compared with control. Reported raw sap consumption decreased in all areas. The reductions in the intervention areas were not significantly greater compared to the control. Respondents directly exposed to the \"only safe sap\" message were more likely to report consuming raw sap from a protected source than those with no exposure (25 vs. 15%, OR 2.0, 95% CI 1.5-2.6, P < 0.001). While the intervention increased knowledge in both intervention areas, the \"only safe sap\" intervention reduced exposure to potentially NiV-contaminated sap and should be considered for future dissemination.
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  • 文章类型: English Abstract
    Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in an outbreak of infection in pigs and humans, and incurred a high fatality rate in humans. We established a system that enabled the rescue of replicating NiVs from a cloned DNA. Using the system, we analyzed the functions of accessory proteins in infected cells and the implications in in vivo pathogenicity. Further, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins, which appeared to be an appropriate to NiV vaccine candidate for use in humans.
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