ACE2

摘要： The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel coronavirus is urgently needed.Citrus fruit peel or wild citrus are rich in flavonoids,and clinically documented for roles in relief of cough and promotion of digestive health.Therefore,citrus fruits are assumed to possess antivirus activities or enhance the host immunity.A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro.We determined six flavonoid compounds’content in three citrus species by using LC-MS technique.The content of naringin and naringenin was at higher levels in pummelo.Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange.The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines(COX-2,iNOS,IL-1βand IL-6)induced by LPS in Raw macrophage cell line,and may restrain cytokine through inhibiting HMGB1 expression in a mouse model.The results revealed that naringin may have a potential application for preventing cytokine storm.We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2(ACE 2),which is a receptor of the coronavirus.Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids,the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.

摘要： 目的基于血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)和适配体CoV2-RBD-1C,结合DNA自组装技术,构建了一种简单、廉价和灵敏的比色传感方法,用于新型冠状病毒刺突蛋白(S蛋白)的检测。方法通过ACE2特异性捕获新型冠状病毒S蛋白,再利用适配体CoV2-RBD-1C将固定探针T固定于S蛋白上,接着,探针T启动X1、X2和L探针的交联聚合形成具有大量DNA双链的DNA纳米枝。最后,利用DNA纳米枝嵌插大量的SYBR Green I(SG)作为信号分子,催化氧化显色底物四甲基联苯胺(tetramethyl benzidine,TMB),实现S蛋白可视化检测。结果成功构建了一种基于ACE2和适配体CoV2-RBD-1C的可视化比色传感方法,其吸光度与S蛋白浓度在5~100ng/mL范围内成正比,检测限(S/N=3)为4.3053ng/mL,具有较高的灵敏度和选择性,已成功用于商业化新型冠状假病毒S蛋白的检测。结论成功构建的可视化比色传感方法,具有廉价、简单、灵敏、便携化、微型化等优点,有望用于新型冠状病毒肺炎(COVID-19)病人的大规模筛查和新冠环境监测。

摘要： Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics.The surface spike protein,which plays a central role in virus infection,is currently the target for vaccines and neutralizing treatments.The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2(ACE2).To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody(mAb)therapies,the binding activities of the original spike protein receptor binding domain(RBD)sequence and the reported spike protein variants were investigated using surface plasmon resonance.In addition,the interactions of the ACE2 receptor,an antispike mAb(mAb1),a neutralizing mAb(mAb2),the original spike RBD sequence,and mutants D614G,N501Y,N439K,Y453F,and E484K were assessed.Compared to the original RBD,the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity,whereas D614G had a substantial reduction in binding affinity.All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD,except for the E484K-mAb1 interaction.The potential neutralizing capability of mAb1 and mAb2 was investigated.Accordingly,mAb1 failed to inhibit the ACE2-RBD interaction while mAb2 inhibited the ACE2-RBD interactions for all RBD mutants,except mutant E484K,which only displayed partial blocking.

摘要： 目的期望获得含有全长hACE2基因序列的hACE2人源化小鼠模型,为心血管疾病、新冠肺炎发病机制研究、药物与疫苗研发提供重要工具。方法将纯化含有hACE2完整编码序列的BAC质粒,利用小鼠受精卵显微注射和输卵管移植技术获得多个首建鼠,分别育种建系,通过杂交育种获得稳定遗传F2代小鼠品系,进一步对F2代小鼠hACE2基因整合、基因拷贝数、相对荧光定量PCR、Western Blot和免疫荧光进行分析。结果育种获得hACE2-6-9、hACE2-14-3、hACE2-15-1和hACE2-15-2共4个小鼠品系。基因整合结果显示,hACE2-6-9、hACE2-15-1和hACE2-15-2小鼠品系含有完整的hACE2基因座位点及较长的基因调控区,hACE2-14-3含有完整的hACE2基因座位点及3’UTR较短的基因调控区。相对荧光定量PCR和Western Blot检测结果显示,hACE2-6-9、hACE2-15-1和hACE2-15-2品系小鼠肠道中hACE2 mRNA和蛋白表达水平较低,而整合较短调控序列的hACE2-14-3小鼠品系则表达水平较高。免疫荧光染色结果显示hACE2-15-1品系小鼠肾小管和肺血管内皮细胞中均有hACE2表达。结论获得了含有全长基因序列的hACE2人源化BAC转基因小鼠,保留完整的hACE2启动子及基因调控区,从而为心血管疾病、新冠肺炎发病机制研究、hACE2基因表达调控机制研究和药物、疫苗的研发提供重要工具。

摘要： Background:The emergence of Coronavirus SARS-CoV-2 evoked an unprecedented threat globally.Ever since the spread of this pandemic research and clinical trials have concentrated on the repurposing of already exciting FDA drugs to find a successful candidate to combat Covid-19.Objective:The objective of this study is to propose a therapeutic protocol that may have a potential solution to treat the severe infections associated with coronavirus.The clinical application of this protocol(Al-Akidi Therapeutic Protocol,A-TP)is highly recommended,as there are several scientific evidences that support this trusted protocol to be of great potential.Methods and Materials:This A-TP includes the use of one of the respiratory Fluoroquinolones(Levofloxacin or Moxifloxacin)in doses of 500 mg twice daily for 7-10 days,together with high doses of Vitamin D3(10000 IU/day)and Zinc(50 mg daily)for few weeks.This protocol is based on the previous antiviral activity of those Fluoroquinolones towards few viruses,the potent antibacterial activity on respiratory infections and high available concentrations in the lungs.It is also based on molecular docking of Levofloxacin and Moxifloxacin on various viral enzymes.Results:Molecular docking showed encouraging and very interesting docking scores and binding affinity of Levofloxacin and Moxifloxacin to certain viral enzymes,such as,RNA dependent RNA polymerase(RdRp),3-Cysteine-Like protease,Neuraminidase,Replicase polyproteins and Trans-Membrane Protease Serine 2 inhibitor(TMPRSS2).The highly expected clinical results of using this protocol are:reduce infection,control of temperature,improve breathing with less dependent on supplemented oxygen,and remarkable reduction of the pro-inflammatory cytokine storm,and hence,reduce hospitalization and mortality.Conclusion:Levofloxacin is highly recommended in managing the severe infections associated with Corona virus and has a remarkable reduction of pro-inflammatory cytokine storm as an immuomodulating agent.Levofloxacin is superior in this protocol over Moxifloxacin,due to its high excretion(≤83%)as unchanged through the kidneys,while Moxifloxacin is only 20%is excreted unchanged.It is an extra advantage of Levofloxacin to manage coronavirus in the kidneys.High doses of Vitamin D3 and Zinc are very useful to provide additional effective measures to combat Corona virus.Therefore,the use of this A-TP is highly and strongly recommended,as it serves the full requirements for excellent and potential therapy for the severe infections associated with Covid-19.

摘要： BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants are currently a new hazard.Since the first appearance of classical SARS-CoV-2 in late 2019,pathogen genetic alterations have continued to occur,and some new hazardous forms have already emerged.The underlying pathophysiological process leading to clinical issue is molecular change caused by genetic mutation.AIM To determine the change in the interaction between receptor binding domain of omicron variant SARS-CoV-2 and the angiotensin-converting enzyme 2(ACE2).METHODS The researchers investigated how alterations in the binding area of the SARS receptor CoV2 interacted electrostatically with the ACE2 receptor.In this report,three important coronavirus disease 2019 variants,beta,delta,and omicron,were investigated.RESULTS According to this study,there was a change of electrostatic interactions between the receptor binding domain of SARS-CoV-2 with the ACE2 receptor due to each studied variant.The most change was detected in omicron variant followed by delta variant and beta variant.CONCLUSION Our results may support the clinical finding that the omicron variant is more transmissible than the wild type and other variants。

摘要： Omicron(B.1.1.529)SARS-CoV-2变种在刺突蛋白中含有异常多的突变,这引起了人们关于Omicron对疫苗、恢复期血清和治疗药物逃逸的担忧。在这里,研究人员分析了Omicron假病毒逃逸血清或治疗抗体中和的程度。两剂BNT162b2疫苗接种3个月后获得的血清样品对Omicron的中和滴度比亲本病毒低18倍。感染Alpha和Delta变种的个体恢复期血清样品允许相似频率的Omicron突破性感染。利用嵌合刺突蛋白的结构域分析表明,这种有效的逃逸主要是通过聚集在受体结合结构域的突变实现的,但N端结构域的多个突变也起了作用。

摘要： A large variety of therapeutic products have been developed as vaccines or treatments of COVID-19 infection. Meanwhile SARS-CoV-2 continues to mutate and spread. The severe COVID-19 patients have limited treatment options. Therefore, mesenchymal stem cells (MSCs) are proposed as another therapeutic target. They are known for their regenerative and immunomodulatory properties. They showed potent efficacy and safety abilities for the treatment of critical COVID-19 patients and intriguing benefits in reducing lungs damage, mortality, and cytokine storm in several clinical studies. Another promising treatment option is the use of dental pulp stem cells (DPSCs) to combat SARS-CoV-2, despite the fact that detailed therapeutic strategies and mechanisms are still lacking. In this review we shed light on the immune response against COVID-19 infection and the relevant knowledge considering the role of MSCs in innate and adaptive immune responses to better understand the immune-physiological mechanisms of MSCs treatment. Lastly, we summarize the latest progress in clinical and research studies suggesting potential MSCs/DPSCs as therapeutic targets in battling COVID-19.

摘要： The coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is threatening public health.The human angiotensin-converting enzyme 2(ACE2)has a remarkably high affinity binding to SARS-CoV-2.This study explored whether certain populations,including obese and cancer patients,are susceptible to SARS-CoV-2.The expression pattern of ACE2 in normal and tumor tissues of cancer patients was compared by the search for network database and re-analysis of pubic data.The level of ACE2 expression in normal adipose tissue was higher than that in normal lung tissue,which indicated the adipose tissue might be vulnerable to SARS-CoV-2;the levels of ACE2 expressed by adipocytes and adipose progenitor cells were similar between non-obese individuals and obese individuals(BMI>29),but obese individuals have more adiposes so as to increase the number of ACE2-expressing cells;the expression of ACE2 in tumor tissues posed by five different types of cancers increased significantly compared with that in adjacent tissues.Therefore,we proposed the following hypothesis:the obese individuals and five types of cancer patients might have a higher risk of SARS-CoV-2 infection,which might become the target population of SARS-CoV-2 infection in the future.

摘要： Children are less susceptible to COVID-19 than adults:they often have asymptomatic and very rarely severe forms.This protection is valid for all variants of the virus.The aim here is to compare the immune response of children with that of adults,asymptomatic adults or those with mild disease with those who develop severe Covid.Several protective factors for children have been mentioned but some of them do not seem to be involved.Indeed,there is no clear difference in the quantity of virus receptors(angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2))present according to age that could explain a lesser entry of the virus into the cells of the nose,oropharynx and lungs of children.In fact,children and adults generally have similar viral loads and respiratory tract excretions.Most adults,like children,have antibodies(and T cells)that cross-react with human coronavirus(HCoVs)and respiratory syndrome coronavirus 2(SARS-CoV-2),but this humoral reactivity does not correlate with disease severity in adults;the difference appears to be more qualitative(IgM and anti-S in children and IgG and IgA and anti-N in adults)than quantitative,and mildly affected adults have some of the characteristics of the cross-reactivities of children.At the cellular level,the difference between children and adults lies more in the naivety of the T cells involved.The amount of salivary and mucosal IgA is negatively correlated with age and positively correlated with the absence of Covid infection:these IgAs are different and more effective than serum IgA.Severe COVID-19 is characterized by hyperinflammation following invasion of the lower respiratory tract when the virus has not been cleared from the upper respiratory tract by innate immunity.Age is associated with an alteration of the immune system,often with a chronic hyperinflammatory state:deficient innate immunity combined with age-related dysregulation of adaptive immunity could cause severe COVID-19.The innate cellular response in the upper and lower airways is more effective in asymptomatic children and adults:the interferon response is earlier and involves immune rather than epithelial cells,the latter being associated with hyperinflammation.This early response is critical given the ability of SARS-CoV-2 to suppress interferon 1(IFN-1)responses.Regulatory Treg cells(which prevent the inflammatory response from spiraling out of control)are prevalent in the respiratory tissues of children.The response of myeloid cells(neutrophils and macrophages/monocytes),which are also responsible for hyperinflammation,is also qualitatively different in mildly affected children and adults compared to severe Covid:there is enrichment of classical monocytes and dysfunctional neutrophils in severe cases.It would be useful to explore why the response of children to SARS-CoV-2 is the opposite of that to influenza virus(which causes classical monocyte influx and overproduction of inflammatory cytokines).Oral dysbiosis is associated with severe COVID-19 and the diversity of the oropharyngeal microbiota is inversely correlated with age.Mycoplasma co-infections amplify viral replication and are associated with severe Covid;children may have more protective anti-mycoplasma IgG because they are more frequently exposed to community infections.The role of hyperinflammation in severe COVID-19 justifies the use of immunomodulatory drugs:hydroxychloroquine,ivermectin,anti-histamines,corticosteroids.Probiotics have been used to restore the gut microbiota that interacts with the lung microbiota.Reduction of the permeability of the intestinal barrier has been proposed.Treatment of immune aging with a prostaglandin inhibitor works well in aged mice by restoring dendritic cell migration.Stimulation of innate immunity by a pathogen recognition motif receptor agonist works in mice.

摘要： 本发明描述ACE抑制剂与N,N'-二苄基乙二胺(简称：N,N'-二苄基乙二胺盐)的新的盐，通过将2摩尔ACE抑制剂与1摩尔N,N'-二苄基乙二胺反应将它们制备为晶体形式和无定形形式的方法，制备含有这些盐的药物配制剂的方法和它们用于治疗心血管疾病的用途。

摘要： 本发明涉及用作脑啡呔酶和ACE抑制剂的某种新的2-取代的1，2-二氢化茚-2-巯基乙酰胺二硫化物衍生物。

摘要： 一种二肽作为ACE酶活性抑制剂的应用。根据已经测定的ACE酶晶体结构，采用分子对接法，利用自研软件对400种二肽的ACE抑制作用进行虚拟筛选，并对虚拟筛选得到的二肽的ACE抑制活性进行实验验证，发现当二肽的N端为半胱氨酸时，二肽具有较好的ACE抑制活性。

摘要： 本发明涉及ACE抑制剂二羧酸与有机胺和/或碱性化合物(alkalicompound)的盐、包含所述盐的透皮治疗系统和制备所述透皮治疗系统的方法。

摘要： 本发明涉及某些可用作脑啡肽酶和ACE抑制剂的新巯基乙酰胺1，3，4，5-四氢苯并[C]氮杂卓-3-酮二硫化物衍生物(通式I)。

摘要： 本发明涉及某些可用作脑啡肽酶和ACE抑制剂的通式(I)新巯基乙酰胺二硫化物衍生物。

摘要： 本发明公开了一种靶向结合ACE2蛋白的ACE2靶向肽及其用途。ACE2靶向肽为多肽，氨基酸序列分别为：FPHWHGNHKHNR、GFKSHFHHNHMR、AHYHRHPPHLNR、LSPHFHHHRGAK、METRPVAPHEFR、LHRPHFHAHNNS、GHQGHWYGMFRA、YPWHHRHMPVHP、SHKHHHWPYHAH、FHGHGSHHNKHR；还包括由微生物、多聚体混合物的表面形成有ACE2靶向肽后的生物活性物质。本发明能够高效靶向ACE2蛋白，阻断新型冠状病毒刺突蛋白与ACE2蛋白的结合，进而起到抑制新型冠状病毒感染的作用。

摘要： 本发明涉及一种以ACE2靶向递送shRNA的ACE2siRNA药物，从冠状病毒保守基因或微卫星中筛选靶标siRNA，由两条互补的正反义siRNA链合成带loop环的小发夹shRNA，并合成以受体结合域RBD为配体的ACE2或穿胞肽ACE2，然后将ACE2分别连接到shRNA的正反义链上，合成由shRNA区和ACE2区构成的ACE2siRNA，其中双价ACE2起中和RBD和靶向递送shRNA的作用，以ACE2桥接的“shRNA‑ACE2‑RBD‑病毒”复合物使shRNA随着病毒的感染进入靶细胞，不但可避免将shRNA非特异性递送给未感染细胞的副作用，而且还能产生抗变异毒株和以ACE2中和病毒的作用，另外以两分子ACE2和1分子shRNA合成的ACE2siRNA及shRNA的免疫佐剂作用可使ACE2具有更强的抗原性，刺激机体产生的抗‑ACE2又具有抗病毒作用。

摘要： 一种提高活性肽ACE抑制率的修饰方法、高ACE抑制率的ACE抑制肽及其应用，属于肽修饰技术领域。本发明对YLVR活性肽进行酶法修饰，修饰后的混合物在0.25mg/mL浓度下的ACE抑制率由52.58％提高至93.56％。根据NANO‑HPLC‑MS/MS鉴定结果，首次发现肽链的N端发生氨基酸聚类会提高肽ACE抑制率，基于此发现，本发明设计了数据库中未被鉴定出的3种高ACE抑制率的ACE抑制肽YLLVR、YYLVR和YYLLVR，经此方法得到的肽活性较高，可作为潜在的降压成分，可以用于制备ACE抑制剂、血管紧张素转换酶抑制剂、降血压药物或具有降血压的功能食品，对资源的综合利用具有极大意义。

摘要： 一种以ACE2靶向递送shRNA的ACE2siRNA药物制备方法，从冠状病毒保守基因或微卫星中筛选靶标siRNA，由两条互补的正反义siRNA链合成带loop环的小发夹shRNA，并合成以受体结合域RBD为配体的ACE2或穿胞肽ACE2，然后将ACE2分别连接到shRNA的正反义链上，合成由shRNA区和ACE2区构成的ACE2siRNA，其中双价ACE2起中和RBD和靶向递送shRNA的作用，以ACE2桥接的“shRNA‑ACE2‑RBD‑病毒”复合物使shRNA随着病毒的感染进入靶细胞，不但可避免将shRNA非特异性递送给未感染细胞的副作用，而且还能产生抗变异毒株和以ACE2中和病毒的作用，另外以两分子ACE2和1分子shRNA合成的ACE2siRNA及shRNA的免疫佐剂作用可使ACE2具有更强的抗原性，刺激机体产生的抗‑ACE2又具有抗病毒作用。