首页 > 最新文献

Clinical Immunology and Immunotherapy最新文献

英文 中文
Supplemental Fetal Calf Serum in T cell Culture Media Expands Bovine Serum Albumin-Specific Human CD4+ T Cells 在T细胞培养基中添加胎牛血清扩增牛血清白蛋白特异性人CD4+ T细胞
Pub Date : 2022-08-10 DOI: 10.24966/ciit-8844/1000072
Weisan Chen
Furthermore, of the 101 synthetic overlapping BSA peptides screened, two HLA-DRB1*01:01-restricted epitopes were identified. Thus, caution should be exercised when FCS-containing culture media is used for T cell clinical trial monitoring
此外,在筛选的101个合成重叠BSA肽中,鉴定出2个HLA-DRB1*01:01-限制性表位。因此,当含有fcs的培养基用于T细胞临床试验监测时,应谨慎使用
{"title":"Supplemental Fetal Calf Serum in T cell Culture Media Expands Bovine Serum Albumin-Specific Human CD4+ T Cells","authors":"Weisan Chen","doi":"10.24966/ciit-8844/1000072","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000072","url":null,"abstract":"Furthermore, of the 101 synthetic overlapping BSA peptides screened, two HLA-DRB1*01:01-restricted epitopes were identified. Thus, caution should be exercised when FCS-containing culture media is used for T cell clinical trial monitoring","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127766048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perceptions and Practices of Social Distancing in Physicians during Covid-19 Pandemic Covid-19大流行期间医生保持社交距离的认识和实践
Pub Date : 2022-01-10 DOI: 10.24966/ciit-8844/1000071
S. Mahmood
Physicians normally have a positive perception about social distancing, but due to personal and work-related factors, compliance to social distancing practices is being found lacking.
医生通常对社交距离有积极的看法,但由于个人和工作相关因素,人们发现对社交距离做法的遵守程度不足。
{"title":"Perceptions and Practices of Social Distancing in Physicians during Covid-19 Pandemic","authors":"S. Mahmood","doi":"10.24966/ciit-8844/1000071","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000071","url":null,"abstract":"Physicians normally have a positive perception about social distancing, but due to personal and work-related factors, compliance to social distancing practices is being found lacking.","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126797264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Essential Impact of Antibodies and Drug Conjugates in Cancer Therapy 抗体和药物偶联物在癌症治疗中的重要作用
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000068
M. Kalim
{"title":"Essential Impact of Antibodies and Drug Conjugates in Cancer Therapy","authors":"M. Kalim","doi":"10.24966/ciit-8844/1000068","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000068","url":null,"abstract":"","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134042203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arthropod-Borne Disease May Lead to a More Resilient Type I Interferon Response to Coronavirus by Reducing Genetic Defects of Innate Immunity by Natural Selection 节肢动物传播的疾病可能通过自然选择减少先天免疫的遗传缺陷,从而导致对冠状病毒更具弹性的I型干扰素反应
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000067
M. Balzan
This article builds on a previous proposal of a hypothesis where- by repeated arthropod or sand-fly vector infection of humans by novel viruses of zoonotic origins carrying bat or mammalian RNA/ DNA, such as phleboviruses may have resulted in the development of an effective evolutionary immune response to most novel zoonotic viruses such as SARS-CoV-2 through survival of the fittest possi bly over many generations. Phleboviruses and Flaviviruses such as Dengue Fever virus (DENV), can infect many mammalian species, including bats and animal husbandry just like coronaviruses. The resulting mutations when crossing species can expose large populations of humans to novel viruses that find the reactive immunity completely unprepared. Survival over thousands of years of human evolution was likely to be dependent on strong and resilient innate immunity, in the form of the Interferon I system. Phleboviruses and Flaviviruses just like Sars-Covid-1 and 2, have multiple biochemical pathways to suppress the IRF3/7 pathway on different levels, which lead to inefficient production of type 1 interferons and an impaired antiviral response. Recently pub-lished research has shown that 3.5% of patients with life-threatening COVID-19 pneumonia had known AR IRF7 and IFNAR1 deficiencies or AD TLR3, TICAM1, TBK1, and IRF3 deficiencies or new (AD UN - C93B1, IRF7, IFNAR1, and IFNAR2 deficiencies) genetic defects in the TLR3- and IRF7-dependent induction and amplification of type I IFNs. In this paper, it is being proposed that populations of the geographical areas of the respective arthropod-borne disease such as phlebovirus or flavivirus infections may have contributed to select within the populations’ survival of individuals free from genetic defects of these pathways. such Lombardy, Kingdom be necessary to support such a hypothesis.
本文建立在先前提出的一个假设的基础上,即通过携带蝙蝠或哺乳动物RNA/ DNA的新型人畜共患病毒(如白蛉病毒)反复感染人类的节肢动物或沙蝇媒介,可能导致通过许多代的适者生存,对大多数新型人畜共患病毒(如SARS-CoV-2)产生有效的进化免疫反应。静脉病毒和黄病毒,如登革热病毒(DENV),可以像冠状病毒一样感染许多哺乳动物物种,包括蝙蝠和畜牧业。跨物种时产生的突变可能会使大量人类暴露于新病毒,而这些病毒发现反应性免疫完全没有准备好。人类几千年的生存进化很可能依赖于强大而有弹性的先天免疫,以干扰素I系统的形式存在。就像sars -1和2一样,静脉病毒和黄病毒有多种生化途径在不同程度上抑制IRF3/7途径,导致1型干扰素产生效率低下,抗病毒反应受损。最近发表的研究表明,3.5%的危及生命的COVID-19肺炎患者已知AR IRF7和IFNAR1缺陷或AD TLR3, TICAM1, TBK1和IRF3缺陷或新的(AD UN - C93B1, IRF7, IFNAR1和IFNAR2缺陷)在TLR3和IRF7依赖性诱导和扩增I型IFNs中存在遗传缺陷。在这篇论文中,有人提出,不同地理区域的节肢动物传播疾病,如白蛉病毒或黄病毒感染,可能对种群中没有这些途径遗传缺陷的个体的生存做出了选择。这样的伦巴第王国有必要支持这样的假设。
{"title":"Arthropod-Borne Disease May Lead to a More Resilient Type I Interferon Response to Coronavirus by Reducing Genetic Defects of Innate Immunity by Natural Selection","authors":"M. Balzan","doi":"10.24966/ciit-8844/1000067","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000067","url":null,"abstract":"This article builds on a previous proposal of a hypothesis where- by repeated arthropod or sand-fly vector infection of humans by novel viruses of zoonotic origins carrying bat or mammalian RNA/ DNA, such as phleboviruses may have resulted in the development of an effective evolutionary immune response to most novel zoonotic viruses such as SARS-CoV-2 through survival of the fittest possi bly over many generations. Phleboviruses and Flaviviruses such as Dengue Fever virus (DENV), can infect many mammalian species, including bats and animal husbandry just like coronaviruses. The resulting mutations when crossing species can expose large populations of humans to novel viruses that find the reactive immunity completely unprepared. Survival over thousands of years of human evolution was likely to be dependent on strong and resilient innate immunity, in the form of the Interferon I system. Phleboviruses and Flaviviruses just like Sars-Covid-1 and 2, have multiple biochemical pathways to suppress the IRF3/7 pathway on different levels, which lead to inefficient production of type 1 interferons and an impaired antiviral response. Recently pub-lished research has shown that 3.5% of patients with life-threatening COVID-19 pneumonia had known AR IRF7 and IFNAR1 deficiencies or AD TLR3, TICAM1, TBK1, and IRF3 deficiencies or new (AD UN - C93B1, IRF7, IFNAR1, and IFNAR2 deficiencies) genetic defects in the TLR3- and IRF7-dependent induction and amplification of type I IFNs. In this paper, it is being proposed that populations of the geographical areas of the respective arthropod-borne disease such as phlebovirus or flavivirus infections may have contributed to select within the populations’ survival of individuals free from genetic defects of these pathways. such Lombardy, Kingdom be necessary to support such a hypothesis.","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116916561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alive and Inactivated Cutibacterium Acnes: Properties, Functions and Pathogenicity 活的和灭活的痤疮表皮杆菌:特性、功能和致病性
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000069
M. Vadalà
{"title":"Alive and Inactivated Cutibacterium Acnes: Properties, Functions and Pathogenicity","authors":"M. Vadalà","doi":"10.24966/ciit-8844/1000069","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000069","url":null,"abstract":"","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121797117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-inflammatory Effect of Peptide LKEKK on Keratinocytes 肽LKEKK对角质形成细胞的抗炎作用
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000064
E. V. Navolotskaya
{"title":"Anti-inflammatory Effect of Peptide LKEKK on Keratinocytes","authors":"E. V. Navolotskaya","doi":"10.24966/ciit-8844/1000064","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000064","url":null,"abstract":"","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129642915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Defective Signal Transduction in Osteoarthritic Chondrocytes and Synovial Fibroblasts Should Become a Target for Drug Intervention 骨关节炎软骨细胞和滑膜成纤维细胞信号转导缺陷应成为药物干预的靶点
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000066
C. Malemud
ry cytokines are an essential driver of synovial joint inflammation in osteoarthritis (OA), drugs [e.g. Anakinra, Tocilizumab, Tofacitinib, Adalibumab] that target the signal transduction pathways activated by these cytokines including, Interleukin-1β (IL-1β), IL-6 and tumor necrosis Factor-α (TNF-α) are routinely employed in the medical therapy of rheumatoid arthritis (RA) [1], but NOT OA. Why is that? Several possible explanations arise from a perusal of the relevant medical literature in the PubMed database. For example, it is well known that genetic and mechanical stressors are integral to the development and progression of OA pathology but the type of inflammation inherent in cartilage destruction in OA was originally classified as “non-classical.” [1]. But is this the case? I think not.
细胞因子是骨关节炎(OA)滑膜关节炎症的重要驱动因素,针对这些细胞因子激活的信号转导途径的药物[如Anakinra, Tocilizumab, Tofacitinib, Adalibumab],包括白细胞介素-1β (IL-1β), IL-6和肿瘤坏死因子-α (TNF-α),常规用于类风湿性关节炎(RA)的药物治疗[1],但不包括OA。为什么呢?通过阅读PubMed数据库中的相关医学文献,可以得到几种可能的解释。例如,众所周知,遗传和机械压力源是骨性关节炎病理发展和进展的组成部分,但骨性关节炎中软骨破坏所固有的炎症类型最初被归类为“非经典”。”[1]。但事实果真如此吗?我不这么认为。
{"title":"Defective Signal Transduction in Osteoarthritic Chondrocytes and Synovial Fibroblasts Should Become a Target for Drug Intervention","authors":"C. Malemud","doi":"10.24966/ciit-8844/1000066","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000066","url":null,"abstract":"ry cytokines are an essential driver of synovial joint inflammation in osteoarthritis (OA), drugs [e.g. Anakinra, Tocilizumab, Tofacitinib, Adalibumab] that target the signal transduction pathways activated by these cytokines including, Interleukin-1β (IL-1β), IL-6 and tumor necrosis Factor-α (TNF-α) are routinely employed in the medical therapy of rheumatoid arthritis (RA) [1], but NOT OA. Why is that? Several possible explanations arise from a perusal of the relevant medical literature in the PubMed database. For example, it is well known that genetic and mechanical stressors are integral to the development and progression of OA pathology but the type of inflammation inherent in cartilage destruction in OA was originally classified as “non-classical.” [1]. But is this the case? I think not.","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126436777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Significance of IGF1R Cell Signaling IGF1R细胞信号传导的治疗意义
Pub Date : 2021-12-31 DOI: 10.24966/ciit-8844/1000065
Xian-Jun Qu
{"title":"Therapeutic Significance of IGF1R Cell Signaling","authors":"Xian-Jun Qu","doi":"10.24966/ciit-8844/1000065","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000065","url":null,"abstract":"","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126205180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Statistical Short-Term Forecasting Of The COVID-19 Pandemic COVID-19大流行的统计短期预测
Pub Date : 2020-12-31 DOI: 10.24966/ciit-8844/1000046
J. Doornik
We have been publishing real-time forecasts of confirmed cases and deaths for COVID-19 from mid-March 2020 onwards, published at www.doornik.com/COVID-19. These forecasts are short-term statistical extrapolations of past and current data. They assume that the underlying trend is informative of short-term developments, without requiring other assumptions of how the SARS-CoV-2 virus is spreading, or whether preventative policies are effective. We provide an overview of the forecasting approach that we use and assess the quality of the forecasts in comparison to those from an epidemiological model.
从2020年3月中旬起,我们一直在www.doornik.com/COVID-19上发布COVID-19确诊病例和死亡人数的实时预测。这些预测是对过去和当前数据的短期统计外推。他们假设基本趋势可以提供短期发展的信息,而不需要对SARS-CoV-2病毒如何传播或预防政策是否有效进行其他假设。我们概述了我们使用的预测方法,并与流行病学模型进行了比较,评估了预测的质量。
{"title":"Statistical Short-Term Forecasting Of The COVID-19 Pandemic","authors":"J. Doornik","doi":"10.24966/ciit-8844/1000046","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000046","url":null,"abstract":"We have been publishing real-time forecasts of confirmed cases and deaths for COVID-19 from mid-March 2020 onwards, published at www.doornik.com/COVID-19. These forecasts are short-term statistical extrapolations of past and current data. They assume that the underlying trend is informative of short-term developments, without requiring other assumptions of how the SARS-CoV-2 virus is spreading, or whether preventative policies are effective. We provide an overview of the forecasting approach that we use and assess the quality of the forecasts in comparison to those from an epidemiological model.","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"94 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124810024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Dominance Of SARS-CoV-2 D614G Variant Explained By The Requirement Of COVID-19 For Calcium; Proximate Therapeutic Implication(S) For COVID-19 COVID-19对钙的需求解释了SARS-CoV-2 D614G变异的优势COVID-19的近似治疗意义(S)
Pub Date : 2020-12-31 DOI: 10.24966/ciit-8844/1000048
Daniel P Cashman
The current dominance of D614G mutation in the SARS-CoV-2 pandemic implies increased infectivity of the virus S protein that drives cellular entry which is triggered by binding to the angiotensin converting enzyme-2 (ACE2) receptor and calcium-dependent protease-mediated activation. Understanding how the D614G spike protein mutation could produce a fitness advantage is key to therapeutic development given its epidemiological dominance. A 14-amino acid (aa) consensus sequence was found in 84 SARS-CoV-2 D614G entries from the NCBI Protein database. No other significant similarity to the D614G mutant sequence was found. A homology to the analogous wild type 14-aa consensus peptide was found in bat coronavirus (APO40579.1) and a smaller 13-aa consensus homology was found with SARS-CoV (AAP41037.1). A successive substring search constrained by the boundary of the D614G consensus peptide compared to all of the proteins in the unbiased Prosite EF-hand calcium-binding domain profile (PS50222) was undertaken because calcium triggers the protease-mediated activation of membrane fusion. A homology to single protein was found; a probable voltage-dependent N-type calcium channel subunit alpha-1B that is involved in the pore-forming regulation of transmembrane calcium transport (Uni Prot KB-P56698). A subsequent brute force Pub Med searching revealed the existence of a laboratory created aspartic acid to glycine mutation in the F protein human parainfluenza virus (hPIV-3 D104G mutation) that facilitated the spread of hPIV-3 in SPCA1 deficient cells. In humans, (SPCA1) regulates the Golgi luminal Ca2+ homeostasis and is ubiquitously expressed in all issues. Decreased SPCA1 expression causes Hailey-Hailey disease, a rare skin disorder that impairs a cells’ ability to transport Ca2+ (i.e., human ATP2C1 gene). Clinically the hypocalcemia associated with hospitalized COVID-19 patients can effectively impair Ca2+ transport in an analogous manner to the SPCA1 deficiency. Here, the D614G SAR-CoV-2 mutant strain can make use of clinical hypocalcemia like the D104G mutated hPIV-3 virus takes advantage of SPCA1 deficient cells to increase infectivity. These data demonstrate the critical importance of calcium for effective SARS-CoV-2/COVID-19 infection and how understanding this mechanism can be exploited for therapeutic gain to stop, or otherwise attenuate virus infection at the earliest steps. Calcium chelation by pharmaceutical EDTA, has been, and can be safely delivered via nebulizer or oral ingestion. EDTA treatment is available in outpatient and inpatient settings and can be self-administered during “quarantine” periods. These proven and safe EDTA treatments should effectively disrupt SARS-CoV-2 spread at the earliest step in the virus lifecycle and warrant investigation and optimization to save lives post haste.
目前,D614G突变在SARS-CoV-2大流行中占主导地位,这意味着病毒S蛋白的传染性增强,该病毒S蛋白通过与血管紧张素转换酶-2 (ACE2)受体结合和钙依赖性蛋白酶介导的激活来驱动细胞进入。考虑到D614G刺突蛋白的流行病学优势,了解D614G刺突蛋白突变是如何产生适应度优势的关键。在NCBI Protein数据库的84个SARS-CoV-2 D614G条目中发现了14个氨基酸的一致序列。没有发现其他与D614G突变序列的显著相似性。在蝙蝠冠状病毒(APO40579.1)和sars冠状病毒(AAP41037.1)中发现了与类似野生型14-aa一致肽同源性较小的13-aa一致肽。由于钙可以触发蛋白酶介导的膜融合激活,因此研究人员对D614G一致肽与无偏Prosite EF-hand钙结合结构域(PS50222)中所有蛋白的边界进行了连续的子串搜索。发现与单个蛋白同源;一个可能的电压依赖性n型钙通道亚基α - 1b,参与钙跨膜运输的成孔调节(Uni Prot KB-P56698)。随后的Pub - Med搜索揭示了在实验室中产生的人副流感病毒F蛋白的天冬氨酸到甘氨酸突变(hPIV-3 D104G突变)的存在,这种突变促进了hPIV-3在SPCA1缺陷细胞中的传播。在人类中,(SPCA1)调节高尔基腔内Ca2+稳态,并在所有问题中普遍表达。SPCA1表达减少导致海利-海利病,这是一种罕见的皮肤疾病,损害细胞运输Ca2+(即人类ATP2C1基因)的能力。在临床上,与住院COVID-19患者相关的低钙血症可以以类似于SPCA1缺乏症的方式有效地损害Ca2+转运。在这里,D614G SAR-CoV-2突变株可以利用临床低钙,就像D104G突变的hPIV-3病毒利用SPCA1缺陷细胞来增加传染性一样。这些数据表明钙对于有效的SARS-CoV-2/COVID-19感染至关重要,以及如何利用这一机制来获得治疗效果,从而在早期阶段阻止或以其他方式减弱病毒感染。药物EDTA的钙螯合作用,已经并且可以安全地通过雾化器或口服摄入。EDTA治疗可在门诊和住院环境中使用,并可在“隔离”期间自行使用。这些经过验证和安全的EDTA治疗方法应该能在病毒生命周期的最初阶段有效地破坏SARS-CoV-2的传播,并有必要进行调查和优化,以在紧急情况下挽救生命。
{"title":"Dominance Of SARS-CoV-2 D614G Variant Explained By The Requirement Of COVID-19 For Calcium; Proximate Therapeutic Implication(S) For COVID-19","authors":"Daniel P Cashman","doi":"10.24966/ciit-8844/1000048","DOIUrl":"https://doi.org/10.24966/ciit-8844/1000048","url":null,"abstract":"The current dominance of D614G mutation in the SARS-CoV-2 pandemic implies increased infectivity of the virus S protein that drives cellular entry which is triggered by binding to the angiotensin converting enzyme-2 (ACE2) receptor and calcium-dependent protease-mediated activation. Understanding how the D614G spike protein mutation could produce a fitness advantage is key to therapeutic development given its epidemiological dominance. A 14-amino acid (aa) consensus sequence was found in 84 SARS-CoV-2 D614G entries from the NCBI Protein database. No other significant similarity to the D614G mutant sequence was found. A homology to the analogous wild type 14-aa consensus peptide was found in bat coronavirus (APO40579.1) and a smaller 13-aa consensus homology was found with SARS-CoV (AAP41037.1). A successive substring search constrained by the boundary of the D614G consensus peptide compared to all of the proteins in the unbiased Prosite EF-hand calcium-binding domain profile (PS50222) was undertaken because calcium triggers the protease-mediated activation of membrane fusion. A homology to single protein was found; a probable voltage-dependent N-type calcium channel subunit alpha-1B that is involved in the pore-forming regulation of transmembrane calcium transport (Uni Prot KB-P56698). A subsequent brute force Pub Med searching revealed the existence of a laboratory created aspartic acid to glycine mutation in the F protein human parainfluenza virus (hPIV-3 D104G mutation) that facilitated the spread of hPIV-3 in SPCA1 deficient cells. In humans, (SPCA1) regulates the Golgi luminal Ca2+ homeostasis and is ubiquitously expressed in all issues. Decreased SPCA1 expression causes Hailey-Hailey disease, a rare skin disorder that impairs a cells’ ability to transport Ca2+ (i.e., human ATP2C1 gene). Clinically the hypocalcemia associated with hospitalized COVID-19 patients can effectively impair Ca2+ transport in an analogous manner to the SPCA1 deficiency. Here, the D614G SAR-CoV-2 mutant strain can make use of clinical hypocalcemia like the D104G mutated hPIV-3 virus takes advantage of SPCA1 deficient cells to increase infectivity. These data demonstrate the critical importance of calcium for effective SARS-CoV-2/COVID-19 infection and how understanding this mechanism can be exploited for therapeutic gain to stop, or otherwise attenuate virus infection at the earliest steps. Calcium chelation by pharmaceutical EDTA, has been, and can be safely delivered via nebulizer or oral ingestion. EDTA treatment is available in outpatient and inpatient settings and can be self-administered during “quarantine” periods. These proven and safe EDTA treatments should effectively disrupt SARS-CoV-2 spread at the earliest step in the virus lifecycle and warrant investigation and optimization to save lives post haste.","PeriodicalId":370947,"journal":{"name":"Clinical Immunology and Immunotherapy","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132524052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
期刊
Clinical Immunology and Immunotherapy
全部 Geobiology Geosci. J. Engineering Science and Technology, an International Journal Org. Geochem. INT J MOD PHYS B Clim. Change Carbon Balance Manage. Communications Earth & Environment 非金属矿 Geol. Ore Deposits ACTA RADIOL "Radiation and Risk" Bulletin of the National Radiation and Epidemiological Registry Global Biogeochem. Cycles Basin Res. Entomologisk tidskrift Atmos. Chem. Phys. Round Table 2011 IEEE 2nd International Conference on Computing, Control and Industrial Engineering Aquat. Geochem. J. Electron. Spectrosc. Relat. Phenom. [Rinsho ketsueki] The Japanese journal of clinical hematology Environ. Pollut. Bioavailability Environmental Progress ENVIRONMENT Espacio Tiempo y Forma. Serie VI, Geografía J. Lumin. High Temp. Acupuncture Research Ocean and Coastal Research ATMOSPHERE-BASEL 2011 IEEE/ACM International Conference on Computer-Aided Design (ICCAD) Administration and Policy in Mental Health and Mental Health Services Research Environ. Toxicol. Pharmacol. EXPERT REV RESP MED JMIR Med. Inf. Acta pharmaceutica Sinica Ore Geol. Rev. 2012 IEEE/RSJ International Conference on Intelligent Robots and Systems Int J Disabil Hum Dev IEEE Magn. Lett. Expert Rev. Mol. Diagn. NANOPHOTONICS-BERLIN Atmos. Meas. Tech. International Journal of Sustainable Development and Planning Contrib. Mineral. Petrol. OCEAN SCI J Perinatology Environ. Eng. Sci. IZV-PHYS SOLID EART+ Zhongguo Yi Miao He Mian Yi COMP BIOCHEM PHYS C J. Hydrol. 航空科学与技术(英文) Geochim. Cosmochim. Acta J. Atmos. Chem. Adv. Atmos. Sci. Acta Geophys. ACTA GEOL SIN-ENGL Int. J. Biometeorol. Appl. Clay Sci. GEOLOGY ACTA PETROL SIN Acta Oceanolog. Sin. Transactions on Electrical and Electronic Materials Big Earth Data ECOTOXICOLOGY Am. Mineral. BIOGEOSCIENCES Adv. Meteorol. Archaeol. Anthropol. Sci. Clean Technol. Environ. Policy Aust. J. Earth Sci. ARCT ANTARCT ALP RES Am. J. Phys. Anthropol. Environ. Chem. Chin. Phys. B Acta Geochimica Best Practice Onkologie ARCHAEOMETRY Energy Environ. Atmos. Res. Am. J. Sci. IEEE Trans. Appl. Supercond. Appl. Geochem. Ecol. Monogr. AAPG Bull. Ann. Glaciol. Environ. Educ. Res, Environ. Mol. Mutagen. Asia-Pac. J. Atmos. Sci. ACTA GEOL POL Environ. Prot. Eng. Nucl. Phys. A Environ. Prog. Sustainable Energy Environ. Technol. Innovation ERN: Other Macroeconomics: Aggregative Models (Topic) ACTA CLIN CROAT Annu. Rev. Earth Planet. Sci. Conserv. Genet. Resour. ECOLOGY
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1