ACE2, angiotensin-converting enzyme 2

ACE2, 血管紧张素转换酶 2
  • 文章类型: Journal Article
    病毒是具有生物活性的寄生虫,仅存在于宿主内部,它们是亚微观水平的。新型冠状病毒病,或COVID-19,通常由SARS-CoV-2病毒引起,与严重急性呼吸道综合症(SARS)相当。由于全球化,随着时间的推移,SARS-CoV-2的自然改变或变化对人类健康产生了重大风险。这些病毒可以在大气中以不同的方式生存和生存,除非它们到达另一个宿主体内。在这个阶段,我们将讨论通过某些环境媒体传播和检测这种致命的SARS-CoV-2病毒的细节,比如大气,水,空气,污水,土壤,温度,相对湿度,和生物气溶胶,为了更好地理解扩散,生存,COVID-19的感染潜力和诊断。
    Viruses are biologically active parasites that only exist inside a host they are submicroscopic level. The novel coronavirus disease, or COVID-19, is generally caused by the SARS-CoV-2 virus and is comparable to severe acute respiratory syndrome (SARS). As a result of globalization, natural alterations or changes in the SARS-CoV-2 have created significant risks to human health over time. These viruses can live and survive in different ways in the atmosphere unless they reach another host body. At this stage, we will discuss the details of the transmission and detection of this deadly SARS-CoV-2 virus via certain environmental media, such as the atmosphere, water, air, sewage water, soil, temperature, relative humidity, and bioaerosol, to better understand the diffusion, survival, infection potential and diagnosis of COVID-19.
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  • 文章类型: Journal Article
    SARS-CoV-2Omicron变体含有15个突变,包括独特的Q493R,在刺突蛋白受体结合域(S1-RBD)中具有高度传染性。虽然与以前报道的突变进行比较提供了一些见解,在BA.4,BA.5,BA.2.75,BQ.1和XBB谱系中观察到的感染增加的潜在机制和独特Q493R突变逆转的影响尚未完全了解.这里,使用结构建模和分子动力学(MD)模拟,我们显示Omicron突变增加了S1-RBD对ACE2的亲和力,而独特的Q493R突变的逆转进一步增加了ACE2-S1-RBD的亲和力.具体来说,我们执行了所有的原子,使用OmicronS1-RBD-ACE2的模型结构进行显式溶剂MD模拟,并将轨迹与WT复合物进行比较,发现OmicronS1-RBD中的Cα原子波动大幅减少,氢键和其他相互作用增加。残基水平分析揭示了几个残基之间相互作用的改变,包括WT复合物中的S1-RBDY449的ACE2D38与Omicron复合物中突变的R残基(Q493R)相互作用的转换。重要的是,用Revertant(无Q493R突变的Omicron)复合物模拟显示S1-RBD和ACE2之间的相互作用进一步增强。因此,本文的结果不仅为Omicron变异体的感染潜力增加提供了见解,而且为逆转某些Omicron谱系中的Q493R突变提供了机制基础,并将有助于理解突变对SARS-CoV-2进化的影响。
    The SARS-CoV-2 Omicron variant containing 15 mutations, including the unique Q493R, in the spike protein receptor binding domain (S1-RBD) is highly infectious. While comparison with previously reported mutations provide some insights, the mechanism underlying the increased infections and the impact of the reversal of the unique Q493R mutation seen in BA.4, BA.5, BA.2.75, BQ.1 and XBB lineages is not yet completely understood. Here, using structural modelling and molecular dynamics (MD) simulations, we show that the Omicron mutations increases the affinity of S1-RBD for ACE2, and a reversal of the unique Q493R mutation further increases the ACE2-S1-RBD affinity. Specifically, we performed all atom, explicit solvent MD simulations using a modelled structure of the Omicron S1-RBD-ACE2 and compared the trajectories with the WT complex revealing a substantial reduction in the Cα-atom fluctuation in the Omicron S1-RBD and increased hydrogen bond and other interactions. Residue level analysis revealed an alteration in the interaction between several residues including a switch in the interaction of ACE2 D38 from S1-RBD Y449 in the WT complex to the mutated R residue (Q493R) in Omicron complex. Importantly, simulations with Revertant (Omicron without the Q493R mutation) complex revealed further enhancement of the interaction between S1-RBD and ACE2. Thus, results presented here not only provide insights into the increased infectious potential of the Omicron variant but also a mechanistic basis for the reversal of the Q493R mutation seen in some Omicron lineages and will aid in understanding the impact of mutations in SARS-CoV-2 evolution.
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  • 文章类型: Journal Article
    当前,迅速多样化的大流行加速了对有效和有效地识别COVID-19潜在候选药物的需求。对SARS-CoV-2感染的宿主免疫应答的知识,然而,仍然有限,迄今为止批准的药物很少。可行的战略和工具正在迅速出现,以解决这一问题,特别是对现有药物的再利用提供了重大的希望。这里我们介绍一个系统生物学工具,表型标志,通过利用可用的转录组学和蛋白质组学数据库,可以对宿主细胞中的SARS-CoV-2感染进行建模,以i)以高灵敏度和特异性(均>96%)确定病毒对细胞宿主免疫反应的影响,产生特定的细胞SARS-CoV-2特征,并且ii)利用这些细胞特异性特征来鉴定有希望的可再利用的疗法。在这个工具的推动下,加上领域专业知识,我们确定了几种潜在的COVID-19药物,包括甲泼尼龙和二甲双胍,并进一步将影响SARS-CoV-2的关键细胞途径识别为COVID-19发病机制的潜在药物靶标。
    The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which -by leveraging available transcriptomic and proteomic databases-allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both>96%) the viral effects on cellular host-immune response, resulting in specific cellular SARS-CoV-2 signatures and ii) utilize these cell-specific signatures to identify promising repurposable therapeutics. Powered by this tool, coupled with domain expertise, we identify several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential druggable targets in COVID-19 pathogenesis.
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  • 文章类型: Journal Article
    严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)是一种高度传染性和致病性病毒,于2019年12月下旬首次出现。这种SARS-CoV-2导致一种称为“冠状病毒传染病-2019”(COVID-19)的急性呼吸道疾病的感染。世界卫生组织(WHO)于2020年3月11日宣布这次SARS-CoV-2疫情是一次大流行。截至2023年1月31日,SARS-CoV-2记录了超过6700万例病例和超过600万人死亡。最近,SARS-CoV的新突变变体也在全球范围内引起了严重的健康问题,未来的小说变体仍然神秘。由于SARS-CoV-2的感染病例每天都在增加,科学家正在尝试使用多种抗病毒药物和针对SARS-CoV-2的疫苗来对抗这种疾病。据我们所知,这是第一次全面总结SARS-CoV-2传播的动态性质,SARS-CoV-2变体(关注的变体和感兴趣的变体),对SARS-CoV-2使用的抗病毒药物和疫苗一目了然。希望,这篇综述将使研究人员获得关于SARS-CoV-2变体和疫苗的知识,这也将为确定针对即将到来的SARS-CoV-2菌株的有效新型疫苗铺平道路。
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic virus that first appeared in late December 2019. This SARS-CoV-2 causes an infection of an acute respiratory disease called \"coronavirus infectious disease-2019 (COVID-19). The World Health Organization (WHO) declared this SARS-CoV-2 outbreak a great pandemic on March 11, 2020. As of January 31, 2023, SARS-CoV-2 recorded more than 67 million cases and over 6 million deaths. Recently, novel mutated variants of SARS-CoV are also creating a serious health concern worldwide, and the future novel variant is still mysterious. As infection cases of SARS-CoV-2 are increasing daily, scientists are trying to combat the disease using numerous antiviral drugs and vaccines against SARS-CoV-2. To our knowledge, this is the first comprehensive review that summarized the dynamic nature of SARS-CoV-2 transmission, SARS-CoV-2 variants (a variant of concern and variant of interest), antiviral drugs and vaccines utilized against SARS-CoV-2 at a glance. Hopefully, this review will enable the researcher to gain knowledge on SARS-CoV-2 variants and vaccines, which will also pave the way to identify efficient novel vaccines against forthcoming SARS-CoV-2 strains.
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  • 文章类型: Journal Article
    研究证据表明,肥胖中的脂肪细胞可能促进SARS-CoV-2的复制,因为它只在超重或肥胖个体的脂肪组织中发现,而在死于COVID-19的瘦个体中没有发现。由于脂质代谢是脂肪细胞功能的关键,和病毒能够利用和操纵宿主细胞的脂质代谢,以获得自身的感染利益,我们假设脂肪细胞不仅能削弱宿主对病毒感染的免疫防御,而且还有助于SARS-CoV-2的进入,复制和组装作为促进肥胖病毒感染的水库。后者主要由SARS-CoV-2劫持脂肪细胞中异常的脂质代谢介导。如果这些被证实,可以考虑通过利用脂肪细胞中异常的脂质代谢来对抗肥胖者的COVID-19的方法,以及改变其他宿主细胞的脂质代谢,作为COVID-19的潜在辅助治疗。
    Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19.
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  • 文章类型: Journal Article
    Lophatherumgracile(L.gracile)长期以来一直被用作功能性食品和草药。以前的研究已经证明,L.gracile的提取物减弱炎症反应和抑制SARS-CoV-2复制;然而,潜在的活性成分尚未确定。本研究调查了L.gracile的生物活性成分。发现L.gracile的黄酮C-糖苷在抗炎和抗病毒作用中占主导地位。开发了一种简单的基于色谱的方法,以从L.gracile中获得富含黄酮C-糖苷的提取物(FlavoLG)。FlavoLG及其主要的黄酮C-糖苷isoorientin被证明可以限制呼吸爆发和激活的人中性粒细胞中中性粒细胞胞外陷阱的形成。FlavoLG和isoorientin还显示通过干扰SARS-CoV-2尖峰在ACE2上的结合来抑制SARS-CoV-2假病毒感染。这些结果提供了科学证据,表明L.gracile作为治疗中性粒细胞相关COVID-19的潜在补充剂的功效。
    Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method was developed to obtain flavone C-glycoside-enriched extract (FlavoLG) from L. gracile. FlavoLG and its major flavone C-glycoside isoorientin were shown to restrict respiratory bursts and the formation of neutrophil extracellular traps in activated human neutrophils. FlavoLG and isoorientin were also shown to inhibit SARS-CoV-2 pseudovirus infection by interfering with the binding of the SARS-CoV-2 spike on ACE2. These results provide scientific evidence indicating the efficacy of L. gracile as a potential supplement for treating neutrophil-associated COVID-19.
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  • 文章类型: Journal Article
    未经批准:SARS-CoV-2感染导致的COVID-19对全球公共卫生产生了巨大的不利影响。随着COVID-19大流行的发展,世界卫生组织宣布了几种令人担忧的变体(VOCs),包括阿尔法,Beta,Gamma,Delta,还有Omicron.与早期的变体相比,Omicron,现在是一个占主导地位的血统,表现出增强的传递性的特征,向性向上呼吸道转移,和减轻疾病的严重程度。尽管疾病严重程度减轻,但Omicron的强劲传播仍然对大流行控制构成了巨大挑战。在这种情况下,其取向转变可用于发现有效的预防措施。
    UNASSIGNED:这篇综述旨在估计绿茶表没食子儿茶素没食子酸酯(EGCG)的潜力,最有效的抗病毒儿茶素,在中和SARS-CoV-2Omicron变体中,基于当前有关EGCG在组织中分布和Omicron向性的知识。
    UNASSIGNED:EGCG具有低生物利用度。饮用绿茶后,血浆EGCG水平在亚微摩尔浓度范围内,或在药物干预后达到最低μM浓度。尽管如此,在饮用绿茶或药物干预后,其在上呼吸道中的浓度可能高达数十甚至数百μM。已经开发了一种在咽部递送足够高浓度的EGCG的方法。令人信服的数据表明,数十至数百μM的EGCG可以显着中和SARS-CoV-2,并有效消除SARS-CoV-2诱导的细胞病变效应和斑块形成。因此,EGCG,在上呼吸道表现出过度积累,鉴于Omicron更倾向于上呼吸道,在当前全球对抗COVID-19的斗争中,作为一种抗病毒药物值得更仔细的研究。
    UNASSIGNED: COVID-19 due to SARS-CoV-2 infection has had an enormous adverse impact on global public health. As the COVID-19 pandemic evolves, the WHO declared several variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and Omicron. Compared with earlier variants, Omicron, now a dominant lineage, exhibits characteristics of enhanced transmissibility, tropism shift toward the upper respiratory tract, and attenuated disease severity. The robust transmission of Omicron despite attenuated disease severity still poses a great challenge for pandemic control. Under this circumstance, its tropism shift may be utilized for discovering effective preventive approaches.
    UNASSIGNED: This review aims to estimate the potential of green tea epigallocatechin gallate (EGCG), the most potent antiviral catechin, in neutralizing SARS-CoV-2 Omicron variant, based on current knowledge concerning EGCG distribution in tissues and Omicron tropism.
    UNASSIGNED: EGCG has a low bioavailability. Plasma EGCG levels are in the range of submicromolar concentrations following green tea drinking, or reach at most low μM concentrations after pharmacological intervention. Nonetheless, its levels in the upper respiratory tract could reach concentrations as high as tens or even hundreds of μM following green tea consumption or pharmacological intervention. An approach for delivering sufficiently high concentrations of EGCG in the pharynx has been developed. Convincing data have demonstrated that EGCG at tens to hundreds of μM can dramatically neutralize SARS-CoV-2 and effectively eliminate SARS-CoV-2-induced cytopathic effects and plaque formation. Thus, EGCG, which exhibits hyperaccumulation in the upper respiratory tract, deserves closer investigation as an antiviral in the current global battle against COVID-19, given Omicron\'s greater tropism toward the upper respiratory tract.
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  • 文章类型: Journal Article
    截至2022年4月,印度已发现超过4300万例COVID-19确诊病例,治愈率为98.8%,导致很大一部分人口,包括医护人员(HCWs),容易发生COVID后遗症。这项研究旨在评估COVID-19感染后医学后遗症的性质和患病率,和风险因素,如果有的话,与他们有关。方法:这是一个观察性的,在8个三级护理中心进行的多中心横断面研究.同意的参与者是COVID-19感染后出院后12-52周的医护人员。人口统计数据,病史,通过具体问卷收集COVID-19的临床特征和COVID后遗症的各种症状。结果:679名合格参与者的平均年龄为31.49±9.54岁。COVID后遗症的总体患病率为30.34%,疲劳(11.5%)是最常见的,其次是失眠(8.5%),活动期间呼吸困难(6%)和关节疼痛(5%)。在患有中度至重度COVID-19的参与者中,有任何后遗症的几率最高(OR6.51;95%CI3.46-12.23),在男性中更低(OR0.55;95%CI0.39-0.76)。除了这些,其他有后遗症的预测因素是年龄(≥45岁),存在任何合并症(尤其是高血压和哮喘),HCW类别(非医生vs医生)和COVID-19导致的住院。解释:大约三分之一的参与者经历了COVID后遗症。COVID疾病的严重程度,女性性别,高龄,合并症是COVID后遗症的重要危险因素。资助:这项工作是印度医学研究委员会(ICMR)-合理使用药物网络的一部分。没有从ICMR获得额外的财政支持来开展这项工作,对于学习材料,医学写作,和APC。通过其合理使用药物的工作组项目资助印度医学研究理事会(ICMR)。
    UNASSIGNED: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any.
    UNASSIGNED: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire.
    UNASSIGNED: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19.
    UNASSIGNED: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae.
    UNASSIGNED: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.
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  • 文章类型: Journal Article
    富含果糖的饮料和食物的消费与心血管疾病的流行上升有关,糖尿病和肥胖。COVID-19的严重程度与这些代谢性疾病有关。富含果糖的食物可能会增加人们患严重COVID-19的风险。我们调查了后代中母体果糖的摄入是否会影响允许SARS-CoV2进入细胞的蛋白质的肝和回肠基因表达。在饮用水中将碳水化合物提供给怀孕的大鼠。成年和年轻的男性后代受到水的影响,液体果糖单独或作为西方饮食的一部分,被研究过。母体果糖降低了年龄较大的后代肝脏SARS-CoV2进入因子的表达。相反,母体果糖促进了西方饮食诱导的年轻后代回肠中病毒进入因子表达的增加。母体果糖摄入产生胎儿程序,增加肝脏病毒保护,相比之下,会加剧果糖加胆固醇诱导的后代小肠SARS-CoV2保护作用的减少。
    Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbohydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol-induced diminution in SARS-CoV2 protection in small intestine of progeny.
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  • 文章类型: Journal Article
    未经证实:病毒感染与自身免疫性疾病的发生有关。最近的报道表明,一部分COVID-19患者会出现严重的多器官损伤疾病。我们评估了COVID-19严重程度之间的关系,抗核和其他系统和器官特异性自身抗体以及SARS-CoV-2感染特异性抗核衣壳(N)IgG抗体和保护性中和抗体(Nab)水平的患病率和持久性。
    UNASSIGNED:对119名根据护理水平分类的COVID-19患者和284名健康受试者的样本进行了抗核和其他全身和器官特异性自身抗体以及SARS-CoV-2和中和抗体水平的存在和持久性的测试。
    UNASSIGNED:数据显示抗RNP-A的水平显着增加,与非ICU护理相比,接受ICU护理的患者中的抗核衣壳和中和抗体。此外,与RNP-A阴性队列相比,接受ICU护理的受试者在RNP-A阳性队列中表现出显著更高的核衣壳IgG水平.值得注意的是,抗RNP-A抗体的表达是短暂的,在症状发作后20至60天之间恢复为非反应性状态。
    未经证实:ICU护理中的COVID-19患者表现出明显更高水平的短暂性RNP-A自身抗体,抗核衣壳,和SARS-CoV-2中和抗体与非ICU患者相比。
    UNASSIGNED: Viral infections have been implicated in the initiation of the autoimmune diseases. Recent reports suggest that a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. We evaluated the relationship between COVID-19 severity, prevalence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 infection specific anti-nucleocapsid (N) IgG antibodies and protective neutralizing antibody (Nab) levels.
    UNASSIGNED: Samples from 119 COVID-19 patients categorized based on their level of care and 284 healthy subjects were tested for the presence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 and neutralizing antibody levels.
    UNASSIGNED: The data shows significantly increased levels of anti RNP-A, anti-nucleocapsid and neutralizing antibody among patients receiving ICU care compared to non-ICU care. Furthermore, subjects receiving ICU care demonstrated significantly higher nucleocapsid IgG levels among the RNP-A positive cohort compared to RNP-A negative cohort. Notably, the expression of anti RNP-A antibodies is transient that reverts to non-reactive status between 20 and 60 days post symptom onset.
    UNASSIGNED: COVID-19 patients in ICU care exhibit significantly higher levels of transient RNP-A autoantibodies, anti-nucleocapsid, and SARS-CoV-2 neutralizing antibodies compared to patients in non-ICU care.
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