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Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na^(+)/H^(+) exchanger
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作者 Medine Cumhur Cure Erkan Cure 《World Journal of Virology》 2023年第1期12-21,共10页
The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely... The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver. 展开更多
关键词 LIVER HEPATOCYTE severe acute respiratory syndrome coronavirus 2 covID-19 Na+/H+exchanger Sodium-proton pump
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Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research
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作者 Shalini Nair Xinguang Chen 《Global Health Journal》 2022年第1期38-43,共6页
Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to... Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity. 展开更多
关键词 severe acute respiratory syndrome coronavirus 2(sars-cov-2) coronavirus disease 2019(covID-19) Immunoresponse Antibody Global health Health policy DECISION-MAKING Serology testing
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A Case of Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 in Pregnancy: A Multidisciplinary Approach
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作者 Kalpana Tyagaraj Ravi Grandhi +3 位作者 Joseph Kim Stanislav Belotserkovskiy Christina Dgheim Dennis Feierman 《Open Journal of Anesthesiology》 2020年第8期284-292,共9页
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patien... Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days. 展开更多
关键词 sars-cov-2 Infection PREGNANCY severe acute respiratory syndrome Multisystem Organ Failure
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Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic 被引量:15
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作者 Shi-Yan Ren Rong-Ding Gao Ye-Lin Chen 《World Journal of Clinical Cases》 SCIE 2020年第4期652-657,共6页
The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to stre... The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions. 展开更多
关键词 coronavirus severe acute respiratory syndrome severe acute respiratory syndrome coronavirus 2 coronavirus disease 2019 OUTBREAK FEAR Discrimination PREJUDICE
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CypA/CD147在SARS-CoV-2感染性心血管疾病诊疗中的作用研究进展
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作者 马明仁 王菲 +2 位作者 蔡晓庆 刘燕 马凌 《解放军医学杂志》 CAS CSCD 北大核心 2024年第1期115-120,共6页
新型冠状病毒感染(COVID-19)疫情当前已得到有效控制,然而其相关并发症仍不容忽视,尤其是心血管循环系统更是新型冠状病毒(SARS-CoV-2)活跃的场所。血管紧张素转换酶2(ACE2)是一种高表达于心脏、肾脏和睾丸的Ⅰ型跨膜糖蛋白,新型冠状病... 新型冠状病毒感染(COVID-19)疫情当前已得到有效控制,然而其相关并发症仍不容忽视,尤其是心血管循环系统更是新型冠状病毒(SARS-CoV-2)活跃的场所。血管紧张素转换酶2(ACE2)是一种高表达于心脏、肾脏和睾丸的Ⅰ型跨膜糖蛋白,新型冠状病毒刺突蛋白通过结合细胞表面受体ACE2入侵宿主细胞,但以此为靶点研发的疫苗、药物在临床应用中仍存在诸多不足。亲环素A(CypA)作为分子伴侣可促进蛋白质折叠及T细胞活化,CD147是研究最为广泛的CypA受体之一,CypA/CD147相互作用在新型冠状病毒进入宿主细胞时发挥重要作用,但新型冠状病毒通过CypA/CD147信号通路入侵心血管系统的研究鲜有报道。基于此,本文在总结前期研究证据并结合课题组研究的基础上,通过对CypA/CD147结构功能、CypA/CD147在心血管疾病中的作用及新型冠状病毒靶向CypA/CD147信号通路引发的心血管疾病进行综述,以期为COVID-19感染并发心血管系统疾病的诊疗提供参考。 展开更多
关键词 亲环素A 细胞外金属蛋白酶诱导剂 新型冠状病毒 心血管系统 心血管疾病
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SARS-CoV-2刺突糖蛋白对神经细胞的损伤效应及机制
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作者 王娇 李佳佳 +3 位作者 肖文一 韦冬晖 蒋宁 周文霞 《中国药理学与毒理学杂志》 CAS 北大核心 2024年第5期375-383,共9页
目的探讨严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突糖蛋白(S蛋白)对人神经母细胞瘤细胞(SH-SY5Y)的损伤效应及其机制。方法用S蛋白0(细胞对照组),25,50,75和100 mg·L^(-1)处理SH-SY5Y 24 h,CCK-8法检测细胞活力;比色法检测乳... 目的探讨严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突糖蛋白(S蛋白)对人神经母细胞瘤细胞(SH-SY5Y)的损伤效应及其机制。方法用S蛋白0(细胞对照组),25,50,75和100 mg·L^(-1)处理SH-SY5Y 24 h,CCK-8法检测细胞活力;比色法检测乳酸脱氢酶(LDH)释放率;EdU试剂盒检测细胞增殖;荧光素酶发光法检测细胞内ATP含量;JC-1荧光探针法检测细胞线粒体膜电位(MMP);Seahorse XF检测细胞糖酵解及线粒体氧化磷酸化水平。结果与细胞对照组相比,S蛋白25,50,75和100 mg·L^(-1)组细胞活力显著降低(P<0.01),半数抑制浓度(IC_(50))为65.05 mg·L^(-1);LDH释放率显著增加(P<0.01);EdU阳性细胞比例显著降低(P<0.01);S蛋白75和100 mg·L^(-1)组细胞内ATP含量显著降低(P<0.01);S蛋白50和75 mg·L^(-1)组细胞内MMP显著降低(P<0.05,P<0.01);S蛋白50 mg·L^(-1)组基础糖酵解水平和糖酵解能力的最大值显著升高(P<0.05,P<0.01),S蛋白25和50 mg·L^(-1)组呼吸能力最大值显著升高(P<0.05,P<0.01)。SH-SY5Y细胞活力与细胞内ATP含量和MMP均呈正相关(r^(2)=0.9209,P=0.001;r^(2)=0.6170,P=0.0025);与反映细胞糖酵解水平的细胞基础糖酵解水平和糖酵解能力最大值呈负相关(r^(2)=0.5194,P=0.0285;r^(2)=0.6664,P=0.0073),与反映线粒体氧化磷酸化水平的ATP生成能力呈负相关(r^(2)=0.8204,P=0.0008)。结论S蛋白使SH-SY5Y细胞活力下降,抑制细胞增殖,其机制可能与干扰神经细胞内能量代谢密切相关。 展开更多
关键词 严重急性呼吸综合征冠状病毒2(sars-cov-2) 刺突糖蛋白 人神经母细胞瘤细胞 神经损伤 糖酵解 能量代谢
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SARS-CoV-2相关儿童急性坏死性脑病的临床、影像特点及预后随访
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作者 刘淑仪 梁泳毅 +6 位作者 高文静 张笑春 吴雪仪 何林超 陈成燕 钟任佳 胡悦林 《新发传染病电子杂志》 2024年第2期11-17,共7页
目的 通过分析10例SARS-CoV-2相关儿童急性坏死性脑病(acute necrotizing encephalopathy,ANE)的临床特点、影像学表现和随访预后情况,提高临床医师对该病的诊疗水平。方法 收集2022年12月至2023年1月广州医科大学附属妇女儿童医疗中心... 目的 通过分析10例SARS-CoV-2相关儿童急性坏死性脑病(acute necrotizing encephalopathy,ANE)的临床特点、影像学表现和随访预后情况,提高临床医师对该病的诊疗水平。方法 收集2022年12月至2023年1月广州医科大学附属妇女儿童医疗中心诊断为SARS-CoV-2相关ANE的10例患儿临床及影像学资料,分析临床表现、实验室指标、治疗过程及颅脑CT或MRI影像学特征,对存活患儿进行半年随访,判断其预后。结果 10例患儿中2例存活,8例死亡。9例患儿首发症状为发热,1例患儿首发症状为呕吐,5例患儿随后出现抽搐症状。8例死亡患儿入院时出现昏迷,从出现症状到昏迷的中位时间为2d,入院格拉斯哥昏迷评分(Glasgow coma scale,GCS)均为重度,ANE严重程度评分(ANE severity scale,ANE-SS)为高风险;2例存活的患儿未出现昏迷症状,入院GCS为轻度及中度,ANE-SS为低风险及中风险。死亡患儿中7例入院时谷丙转氨酶升高,8例谷草转氨酶升高,7例合并肺部感染;存活患儿中,1例谷丙转氨酶与谷草转氨酶正常,另1例谷草转氨酶升高,谷丙转氨酶正常,2例均未见肺部感染。所有的病例均累及丘脑及脑干,同时可累及基底节、侧脑室旁白质、双侧额顶叶和小脑,与其他感染源引起的急性坏死性脑病影像学表现相仿,CT和MRI显示多灶性对称性改变,CT为低密度改变,部分有出血征象;MRI增强扫描可见病灶强化,弥散加权序列弥散受限,预后差且诊断脑死亡的患儿MRI增强未见脑内血管造影剂显影,预后良好的患儿复查病灶逐渐减少消失。结论 儿童因感染SARS-CoV-2发生的ANE,应当及时识别并且积极治疗,CT及MRI检查均能显示对称性病变,而MRI检查对早期发病更敏感。 展开更多
关键词 新型冠状病毒 急性坏死性脑病 儿童 影像 预后
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Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model 被引量:1
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作者 Wei-ming YAN  Jia-quan HUANG  +1 位作者 Xiao-ping LUO Qin NING 《中国病毒学》 CSCD 2007年第3期181-192,共12页
To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) thro... To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage. 展开更多
关键词 凝血酶原酶 fg12基因 肺损伤 急性呼吸综合征 基因表达
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SARS-CoV-2细胞受体的研究进展
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作者 陈生林 肖蔓 +5 位作者 李赵忠 徐志凯 韩起 冯东方 邓雁 殷作明 《微生物与感染》 CAS 2023年第1期46-54,共9页
严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)是引起2019冠状病毒病(coronavirus disease 2019,COVID-19)的病原体,在人群中广泛持久传播,对人类健康和社会经济造成了巨大危害。目前,针对... 严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)是引起2019冠状病毒病(coronavirus disease 2019,COVID-19)的病原体,在人群中广泛持久传播,对人类健康和社会经济造成了巨大危害。目前,针对COVID-19的治疗尚无特异高效的抗病毒药物。病毒为实现寄生感染,通常先与宿主细胞膜表面受体结合,进而内化入胞。因此,SARS-CoV-2受体决定着病毒的感染特性和宿主范围,对其进行研究和解析是战胜SARS-CoV-2感染的一个关键手段。SARS-CoV-2受体的发现和鉴定,将为COVID-19提供新的治疗靶点。本文主要对SARS-CoV-2入侵受体及黏附受体的研究进展进行综述。 展开更多
关键词 严重急性呼吸综合征冠状病毒2 入侵 受体 黏附受体 刺突蛋白 受体结合域
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Clinical and Spatial Characteristics of Severe Acute Respiratory Syndrome by COVID-19 in Indigenous of Brazil
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作者 Daniele Melo Sardinha Karla Valéria Batista Lima +7 位作者 Ana Lúcia da Silva Ferreira Juliana Conceição Dias Garcez Thalyta Mariany Rêgo Lopes Ueno Yan Corrêa Rodrigues Anderson Lineu Siqueira dos Santos Rosane do Socorro Pompeu de Loiola Ricardo José de Paula Souza e Guimarães Luana Nepomuceno Gondim Costa Lima 《Advances in Infectious Diseases》 2021年第4期441-454,共14页
The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The dise... The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O<sub>2</sub> saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O<sub>2</sub> saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population. 展开更多
关键词 severe acute respiratory syndrome Indigenous People sars-cov-2 covID-19 Brazil
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Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases
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作者 Feibao CHEN Changming ZHANG +6 位作者 Chen CHEN Ping JI Chanjuan ZHANG Yanbo LI Hao WANG Baobao GU Yanting YANG 《Medicinal Plant》 2024年第2期61-64,共4页
[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362... [Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection. 展开更多
关键词 severe acute respiratory syndrome coronavirus 2 infection Asymptomatic Mild/common Yinhuang Qingfei capsules
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靶向SARS-CoV-2受体结合结构域的嵌合抗体表达及功能研究
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作者 石慧春 焦凡珂 +3 位作者 徐巍 陈永康 陆路 邹鹏 《微生物与感染》 CAS 2023年第1期2-12,共11页
严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染所致的2019冠状病毒病(coronavirus disease 2019,COVID-19)给人民的生命健康造成了严重的威胁,目前该病毒仍然在广泛传播,针对SARS-CoV-... 严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染所致的2019冠状病毒病(coronavirus disease 2019,COVID-19)给人民的生命健康造成了严重的威胁,目前该病毒仍然在广泛传播,针对SARS-CoV-2有效的治疗方法仍有限,因此寻找广谱中和抗体阻断SARS-CoV-2感染具有重要的意义。本文成功表达并纯化了3株靶向SARS-CoV-2的受体结合结构域(receptor-binding domain,RBD)的人鼠嵌合抗体,并且检测了这几株抗体对多种SARS-CoV-2假病毒和活病毒的中和活性。本研究表明这3株抗体能特异性地中和SARS-CoV-2野生型假病毒,IC 50分别为0.03μg/mL、0.06μg/mL、0.03μg/mL。此外,这3株抗体对Alpha株假病毒、Delta株假病毒和Lambda株假病毒也具有广谱中和活性,并可以抑制SARS-CoV-2 Delta株活病毒的复制。机制研究表明,这些抗体可以阻断SARS-CoV-2的S蛋白介导的细胞-细胞融合,且RBD上的K417、E484和N501位点可能是其与这3株抗体结合的关键位点。 展开更多
关键词 严重急性呼吸综合征冠状病毒2 受体结合结构域 嵌合抗体 中和抗体
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基于PPI分析新型冠状病毒(SARS-CoV-2)受体ACE2在高血压靶点中的网络关联影响
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作者 吴佳芸 李玲玲 +2 位作者 朱春临 姚睿祺 黄力 《中国循证心血管医学杂志》 2023年第2期150-156,共7页
目的基于PPI网络探讨新型冠状病毒(SARS-CoV-2)受体ACE2在高血压靶点中的网络关联影响及相互作用关系,为临床治疗COVID-19合并高血压提供理论参考。方法从GeneCards、DisGnet、OMIM和TTD数据库检索高血压靶点,通过关联分数筛选重要靶点... 目的基于PPI网络探讨新型冠状病毒(SARS-CoV-2)受体ACE2在高血压靶点中的网络关联影响及相互作用关系,为临床治疗COVID-19合并高血压提供理论参考。方法从GeneCards、DisGnet、OMIM和TTD数据库检索高血压靶点,通过关联分数筛选重要靶点,将所得靶点统一导入String平台,得到蛋白相互作用(PPI)网络,利用Cytoscape3.8.0筛选与ACE2最为直接相关的靶点后,再次通过String数据库获取新的PPI网络,提取该网络中的核心蛋白功能模块,并完成GO、KEGG富集分析。参考ACE2在各模块中的评分结果,分析其在整体网络结构中的影响意义和关联。结果最终从高血压靶点中筛选得到33个与ACE2直接相关的蛋白,通过聚类分析发现它们共聚集形成了3个功能模块,主要涉及的生物学功能是管径调节、激素水平调节与内分泌调节,分子功能分别是执行调控受体调节子活性、外肽酶活性与激素活性,而主要富集的通路有神经活性配体受体相互作用、肾素-血管紧张素系统信号转导途径等。评分结果显示,ACE2所在模块内评分较高的是ACE2、CAT、DPP4、ACHE、CMA1,提示它们对其他蛋白模块的影响可能更大;而在跨模块关联分析中则发现AGT、AGTR1、EDN1、ALB与AGTR2评分较高,说明上述蛋白可能是模块3与其他模块发生相互作用的关键节点。结论ACE2在高血压靶点网络中占据重要地位,而RAS是连接COVID-19与高血压病的核心枢纽,其失衡是引起单纯COVID-19患者发生血压升高或COVID-19合并高血压出现高致死率的关键所在。ACE2通过与CAT、ACHE、CMA1、EDN1等蛋白的交互作用参与升高血压,同时与COVID-19相联系,但其上调是否有助于SARS-CoV-2入侵以及ACEI、ARB类在合并高血压的COVID-19患者的应用仍有待验证。 展开更多
关键词 ACE2 sars-cov-2 高血压 跨模块关联 网络影响评价
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基于分子对接和分子动力学模拟技术筛选SARS-CoV-23CL蛋白酶抑制剂
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作者 吉冰洁 李尚校 +3 位作者 王俭 边远 刘浩 赵勇山 《沈阳药科大学学报》 CAS CSCD 北大核心 2023年第8期1069-1077,1091,共10页
目的 以分子对接和分子动力学模拟技术相结合的方法筛选得到严重急性呼吸系统综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2,SARS-CoV-2) 3CL蛋白酶的小分子抑制剂。方法 基于SARS-CoV-2 3CL蛋白酶的晶体结构(PDB ... 目的 以分子对接和分子动力学模拟技术相结合的方法筛选得到严重急性呼吸系统综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2,SARS-CoV-2) 3CL蛋白酶的小分子抑制剂。方法 基于SARS-CoV-2 3CL蛋白酶的晶体结构(PDB ID:7K3T和7SI9),从PubChem数据库中筛选得到SARS-CoV-2 3CL蛋白酶的特异性抑制剂nirmatrelvir的结构类似物,使用Autodock进行非共价分子对接,使用AutoDockFR进行共价分子对接,采用Pymol和Ligplot软件对SARS-CoV-2 3CL蛋白酶和小分子进行相互作用模式分析,最后使用AMBER18进行小分子化合物与SARS-CoV-2 3CL蛋白酶复合物的分子动力学模拟,进一步验证分子对接结果,使用SwissADME对化合物进行成药性分析。结果 将78个nirmatrelvir结构类似物与SARS-CoV-2 3CL蛋白酶进行虚拟筛选和分子对接,得到了2个与nirmatrelvir作用相当的小分子化合物(PubChem ID:57842182和156619968),共价对接发现化合物57842182和化合物156619968与SARS-CoV-2 3CL蛋白酶间不存在共价结合。分子动力学模拟结果表明化合物57842182、化合物156619968与SARS-CoV-2 3CL蛋白酶的结合自由能(ΔE_(total))分别为-23.96 kcal·mol^(-1)和-27.11 kcal·mol^(-1),二者主要通过与MET165、GLU166、ASN142、CYS145、LEU50、MET49等氨基酸残基的相互作用占据SARS-CoV-2 3CL蛋白酶亚活性位点,具有潜在抑制SARS-CoV-2 3CL蛋白酶活性的功能。化合物57842182和化合物156619968的成药性略差于nirmatrelvir。结论 筛选得到的nirmatrelvir结构类似物57842182和156619968具有作为新型冠状病毒SARS-CoV-2 3CL蛋白酶小分子抑制剂的潜力,其与SARS-CoV-2 3CL蛋白酶的结合特点可为SARS-CoV-2 3CL蛋白酶抑制剂的药物设计提供线索。 展开更多
关键词 新型冠状病毒 sars-cov-23CL蛋白酶 分子对接 分子动力学模拟
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计算机模拟纳豆源多肽与DPP-IV和SARS-CoV-2Mpro的相互作用
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作者 曾巧辉 郭槟勇 +4 位作者 高立芳 黄燕燕 王敬敬 曾新安 彭名军 《现代食品科技》 CAS 北大核心 2023年第6期142-153,共12页
兼具糖尿病的新型冠状病毒肺炎(Corona Virus Disease2019,COVID-19)患者病死率明显偏高,抑制Ⅱ型糖尿病关键酶二肽基肽酶4(DPP-IV)和新冠肺炎病毒主蛋白酶(SARS-CoV-2 Mpro)的活性能缓解相应的病症。该研究采用UniProt、NCBI和PDB数据... 兼具糖尿病的新型冠状病毒肺炎(Corona Virus Disease2019,COVID-19)患者病死率明显偏高,抑制Ⅱ型糖尿病关键酶二肽基肽酶4(DPP-IV)和新冠肺炎病毒主蛋白酶(SARS-CoV-2 Mpro)的活性能缓解相应的病症。该研究采用UniProt、NCBI和PDB数据库检索纳豆蛋白,基于BIOPBP-UWM数据库开展计算机模拟胃肠道蛋白酶(胃蛋白酶、胰蛋白酶和胰凝乳蛋白酶)水解纳豆蛋白的研究,最后利用分子对接技术分别研究纳豆蛋白源多肽与DPP-IV和SARS-CoV-2 Mpro的结合能力,分析参与相互作用的氨基酸残基与分子作用力类型。结果发现,糖转运蛋白与两种酶具有良好的结合效果。特别地,序列为ISQPR、TIPVR和STVTR的多肽对两种酶都具有较高的结合分数(≤-130),被鉴定为DPP-IV和SARS-CoV-2Mpro的双重抑制肽。因此,纳豆蛋白具有缓解Ⅱ型糖尿病病症和作为新型冠状病毒感染病人营养补充剂的潜力。 展开更多
关键词 二肽基肽酶-IV 新冠肺炎主蛋白酶 纳豆蛋白 营养补充
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SARS-CoV-2抗原快速检测方法的研究进展 被引量:1
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作者 岳彩蝶 李军燕 +2 位作者 丁爱军 谢力 曾韦锟 《检验医学》 CAS 2023年第1期87-93,共7页
新型冠状病毒(SARS-CoV-2)感染的大流行导致了一场全球性的健康危机。快速、准确地检出SARS-CoV-2是明确感染规模并采取进一步干预措施的重要前提。病毒核酸检测是新型冠状病毒肺炎(COVID-19)确诊的标准方法,在一些特殊场景下,即时检验(... 新型冠状病毒(SARS-CoV-2)感染的大流行导致了一场全球性的健康危机。快速、准确地检出SARS-CoV-2是明确感染规模并采取进一步干预措施的重要前提。病毒核酸检测是新型冠状病毒肺炎(COVID-19)确诊的标准方法,在一些特殊场景下,即时检验(POCT)是必要的补充。文章对用于SARS-CoV-2抗原检测的POCT方法的标记物(胶体金、乳胶微球、荧光物质、量子点和酶)和基于不同方法构建的各种类型的传感器进行总结,以期为SARS-CoV-2检测试剂的研发提供参考。 展开更多
关键词 新型冠状病毒 新型冠状病毒肺炎 即时检验 抗原检测
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Temporal and Spatial Distribution of SARS-CoV-2 Aerosols in a Large-Scale Fangcang Shelter Hospital in Shanghai,China
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作者 Jiafu Jiang Zhe Yin +23 位作者 Jing Li Leili Jia Rulin He Wenhui Yang Jihu Yang Hang Fan Sen Zhang Yunfei Wang Zengming Zhao Haoran Peng Lizhong Li Yi Yang Shi-Yong Fan Rong Xiang Jianshu Guo Jinjin Wang Juanning Wei Fengling Zhou Ding Liu Ping Zhao Yujun Cui Yunxi Liu Dongsheng Zhou Gang Dong 《Engineering》 SCIE EI CAS CSCD 2023年第9期222-233,共12页
The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmi... The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse.During the COVID-19 pandemic in Shanghai,China in 2022,samples were collected in a Fangcang shelter hospital,a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center(Shanghai)into a health care facility.Aerosol samples at different sites and intervals around patients and in public areas,surface samples,and pharyngeal swab samples from corresponding patients were included.Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction(RT-qPCR)assays,followed by sequencing if the cycle threshold(Ct)value was<30.The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones(37.5%,104/277),especially around the bed(41.2%,68/165)and near ventilation inlets(45.2%,14/31).The prevalence of SARS-CoV-2 around the bed,public areas,and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites.Some surface samples of different personal protective equipment from medical staff had high positivity rates.Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2.There was consistency in virus sequences from the same patient and their environment,and the detected virus sequences matched those of virus strains in circulation during the collection periods,which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital.In summary,the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital. 展开更多
关键词 coronavirus disease 2019 severe acute respiratory syndrome coronavirus 2 AEROSOLS Fangcang shelter hospital China
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The protection of CoronaVac against the infection of wild-type SARS-CoV-2(WH-09)or Omicron variant in nude-hACE2 mice
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作者 Kaili Lin Meixuan Liu +5 位作者 Lu Sun Hanjun Fu Hongwei Qiao Shunyi Wang Sidan Pan Hong Gao 《Animal Models and Experimental Medicine》 CAS CSCD 2023年第4期346-354,共9页
Background:Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and severe outcomes,but we pay less attention to these people.Athymic nude mice a... Background:Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and severe outcomes,but we pay less attention to these people.Athymic nude mice are a murine strain with a spontaneous deficiency of the Foxn1 gene,which can result in thymic degeneration or its absence,leading to immunosuppression and a decrease in the number of T cells,and are widely used in preclinical evaluations of disease in immunocompromised populations.Methods:We investigated the protection of the coronavirus disease 2019(COVID-19)inactivated vaccine(CoronaVac)against the infection of wild-type SARS-CoV-2(WH-09)or Omicron variant utilizing a hybrid-type nude-hACE2 mouse model.Results:Compared with nude-hACE2/W mice,the viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/WV)infected with WH-09 after vaccination significantly decreased,and the histopathological changes were also reduced.The viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/OV)infected with the Omicron variant after vaccination was lower than that in nude-hACE2/O,but histopathological symptoms did not improve significantly.Conclusion:CoronaVac provides some protection against infection of both WH-09 and the Omicron variant in the nude-hACE2 mice.Our findings aimed to provide a reference for vaccination against SARS-CoV-2 in immunocompromised populations. 展开更多
关键词 IMMUNOCOMPROMISED nude-hACE2 mice PROTECTION severe acute respiratory syndrome coronavirus 2
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COVID-19患者SARS-CoV-2感染前后精液质量参数变化的meta分析
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作者 杨磊 冯美宁 +2 位作者 宋海锋 杨进 许涛 《现代检验医学杂志》 CAS 2023年第1期179-185,共7页
目的分析新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染前后精液质量参数的变化。方法计算机检索PubMed,Embase,中国知网、... 目的分析新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染前后精液质量参数的变化。方法计算机检索PubMed,Embase,中国知网、万方和维普数据库,筛选有关COVID-19患者SARS-CoV-2感染前后精液质量参数变化的文献,检索时间为2019年12月~2022年8月5日。文献质量采用NOS评分。统计分析采用StataSE15.0软件,根据SARSCoV-2感染后精液检测时间进行亚组分析、敏感度分析评估结果的稳定性。结果纳入6篇COVID-19患者SARSCoV-2感染前后的自身对照文献,样本量为21~100例。SARS-CoV-2感染后精液质量参数与感染前相比,总活动精子率[SMD=-0.73,95%CI(-1.16~-0.30)]和前向运动精子率[SMD=-0.52,95%CI(-0.87~-0.17)]下降,差异均有统计学意义(Z=-3.356,-2.932,P=0.001,0.003)。亚组分析显示,SARS-CoV-2感染三个月后精液质量参数与感染前相比,精液量[SMD=-0.15,95%CI(-0.70~0.40)]、精子浓度[SMD=-0.15,95%CI(-0.43~0.13)]、总活动精子率[SMD=-0.85,95%CI(-1.87~0.18)]和前向运动精子率[SMD=-0.48,95%CI(-1.13~0.17)]差异均无统计学意义(Z=-1.622~-0.522,均P>0.05)。敏感度分析精液参数结果稳定。结论初步研究发现COVID-19患者精液质量短期内可能存在不良影响,三个月后可以恢复。 展开更多
关键词 新型冠状病毒肺炎 严重急性呼吸综合征冠状病毒2 精液质量参数 META分析
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SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients
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作者 Wattana Leowattana Tawithep Leowattana Pathomthep Leowattana 《World Journal of Meta-Analysis》 2022年第4期195-205,共11页
Due to the disease's broad clinical spectrum,it is currently unclear how to predict the future prognosis of patients at the time of diagnosis of coronavirus disease 2019(COVID-19).Real-time reverse transcription-p... Due to the disease's broad clinical spectrum,it is currently unclear how to predict the future prognosis of patients at the time of diagnosis of coronavirus disease 2019(COVID-19).Real-time reverse transcription-polymerase chain reaction(RTPCR)is the gold standard molecular technique for diagnosing COVID-19.The number of amplification cycles necessary for the target genes to surpass a threshold level is represented by the RT-PCR cycle threshold(Ct)values.Ct values were thought to be an adequate proxy for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral load.A body of evidence suggests that SARS-CoV-2 viral load is a possible predictor of COVID-19 severity.The link between SARS-CoV-2 viral load and the likelihood of severe disease development in COVID-19 patients is not clearly elucidated.In this review,we describe the scientific data as well as the important findings from many clinical studies globally,emphasizing how viral load may be related to disease severity in COVID-19 patients.Most of the evidence points to the association of SARS-CoV-2 viral load and disease severity in these patients,and early anti-viral treatment will reduce the severe clinical outcomes. 展开更多
关键词 severe acute respiratory syndrome coronavirus-2 Viral load Upper respiratory tract coronavirus disease 2019 patients Disease severity Clinical outcome
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