Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the n...Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the nearest family member of the virus and its receptor binding domain of S protein including its model structure and function of its active sites were naked through Multiple Sequence Alignment, modelling and molecular docking software accordingly its repository genome databases. The virus was genetically associated and molecular evolutionary related with (<em>RaTG</em>13) and it scores 96.12% homology with 99% query coverage followed by <em>bat-SL-CoVZC</em>45 and<em> bat-SL-CoVZXC</em>21 notch 89.12% and 88.65% respectively. However, SARS and MERS corona type virus those outbreak earlier respectively less likely family members of 2019-nCoV. Though the virus has a close genetic association with those previous SARS coronaviruses, and certainly the spike protein used as a binding receptor to fight against human receptor protein of ACE 2, but on the basis of FRODOC and HDOCK server analysis multi favorable active sites of S protein was discovered such GLN493 shown as a finest key in both model and possessed a unique traits on it resulting unexpected rate of transmission and number of people died while compared to the previous one. TYR500, ASN501, GLN498 and others residues preferably contemplate site also. In particular, the diversity of the virus in the world may be due to the genome structure of the virus and S gene changed over the time, across the world against to host of human genetic diversity, which may be more robust, and may be a new and unique feature. This is because it is characterized close to contact with distance divergence between wild type novel coronavirus which was risen from China against to the genomes from Lebanon, India, Italy, and USA and so on. Thus, the World Health Organization and its researchers should focus on immunologic research and effective drug and vaccine development that will help to address the epidemiology of the virus, which can provide a long-term solution.展开更多
目的:通过生物信息学方法分析血管紧张素转化酶2(ACE2)的基因及蛋白,为深入揭示该基因的疾病机理和相关药物研发提供参考。方法:分别选用DNASTAR、ExPASy、SOPMA等生物信息学平台分别对ACE2的基因蛋白信息及功能进行分析。结果:人源ACE...目的:通过生物信息学方法分析血管紧张素转化酶2(ACE2)的基因及蛋白,为深入揭示该基因的疾病机理和相关药物研发提供参考。方法:分别选用DNASTAR、ExPASy、SOPMA等生物信息学平台分别对ACE2的基因蛋白信息及功能进行分析。结果:人源ACE2基因编码区长2418 bp,编码805个氨基酸。人源ACE2蛋白分子式为C 4170 H 6358 N 1092 O 1222 S 35,相对分子质量为92463.04,体外不稳定,二级结构以α螺旋和无规则卷曲为主,存在1个跨膜结构,信号肽位于17~18 bp处,有77个磷酸化位点和7个N-糖基化位点,存在37个B细胞抗原表位。通过String数据库得到蛋白相关功能和通路,发现ACE2蛋白在RAS系统、蛋白质消化吸收、肾素分泌和心肌细胞中的肾上腺素信号传导信号通路中发挥着重要作用,是血小板相关生物过程的重要部分。同源性分析和进化树显示灵长类动物与人类ACE2蛋白相似性最高。结论:利用生物信息学方法研究人源ACE2基因和蛋白的基本结构、性质、功能,为新型冠状病毒患者出现的症状机理提供一定的理论支持,对进一步探索疾病发生机制和药物研发提供参考。展开更多
Background Growing epidemiologic evidence has indicated that genetics can predispose individuals to the occurrence of lone atrial fibrillation (AF). The angiotensin-converting enzyme 2 (ACE2) gene has been establi...Background Growing epidemiologic evidence has indicated that genetics can predispose individuals to the occurrence of lone atrial fibrillation (AF). The angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with hypertension and left ventricular hypertrophy. The objective of our study was to investigate the association of ACE2 gene polymorphisms with lone AF. Methods A total of 265 consecutive lone AF patients and 289 healthy controls were successfully investigated. The polymorphisms rs2106809 and rs2285666 were genotyped by polymerase chain reaction (PCR) and direct sequencing. A Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CO of variations of ACE2 for lone AF. Results The T allele of rs2106809 conferred an increased risk for lone AF (OR 1.24, 95% CI 1.01-1.52, P=0.03) in males after adjustment for conventional risk factors. SNP at rs2285666 in males was not significantly different between AF patients and controls. No association was found between the two polymorphisms in the female population with lone AF. After (36.3±4.5) months of follow-up, the end point data were obtained: death (cardiac and noncardiac), ischemic stroke, and heart failure. In the male subgroup, the associations between rs2106809 T male carriers and combined end points including ischemic stroke, heart failure, and death in our study were of significance (OR 3.6, 95% CI 1.0-13.1, P=-0.04). Conclusions The results indicate that polymorphism at ACE2 gene is associated with male lone AF in a Chinese Han population. Lone AF males who c.arrv the. rs2106809T alle.le, are. associate.d with adverse cardiac, e.ve.nts展开更多
文摘Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the nearest family member of the virus and its receptor binding domain of S protein including its model structure and function of its active sites were naked through Multiple Sequence Alignment, modelling and molecular docking software accordingly its repository genome databases. The virus was genetically associated and molecular evolutionary related with (<em>RaTG</em>13) and it scores 96.12% homology with 99% query coverage followed by <em>bat-SL-CoVZC</em>45 and<em> bat-SL-CoVZXC</em>21 notch 89.12% and 88.65% respectively. However, SARS and MERS corona type virus those outbreak earlier respectively less likely family members of 2019-nCoV. Though the virus has a close genetic association with those previous SARS coronaviruses, and certainly the spike protein used as a binding receptor to fight against human receptor protein of ACE 2, but on the basis of FRODOC and HDOCK server analysis multi favorable active sites of S protein was discovered such GLN493 shown as a finest key in both model and possessed a unique traits on it resulting unexpected rate of transmission and number of people died while compared to the previous one. TYR500, ASN501, GLN498 and others residues preferably contemplate site also. In particular, the diversity of the virus in the world may be due to the genome structure of the virus and S gene changed over the time, across the world against to host of human genetic diversity, which may be more robust, and may be a new and unique feature. This is because it is characterized close to contact with distance divergence between wild type novel coronavirus which was risen from China against to the genomes from Lebanon, India, Italy, and USA and so on. Thus, the World Health Organization and its researchers should focus on immunologic research and effective drug and vaccine development that will help to address the epidemiology of the virus, which can provide a long-term solution.
文摘目的:通过生物信息学方法分析血管紧张素转化酶2(ACE2)的基因及蛋白,为深入揭示该基因的疾病机理和相关药物研发提供参考。方法:分别选用DNASTAR、ExPASy、SOPMA等生物信息学平台分别对ACE2的基因蛋白信息及功能进行分析。结果:人源ACE2基因编码区长2418 bp,编码805个氨基酸。人源ACE2蛋白分子式为C 4170 H 6358 N 1092 O 1222 S 35,相对分子质量为92463.04,体外不稳定,二级结构以α螺旋和无规则卷曲为主,存在1个跨膜结构,信号肽位于17~18 bp处,有77个磷酸化位点和7个N-糖基化位点,存在37个B细胞抗原表位。通过String数据库得到蛋白相关功能和通路,发现ACE2蛋白在RAS系统、蛋白质消化吸收、肾素分泌和心肌细胞中的肾上腺素信号传导信号通路中发挥着重要作用,是血小板相关生物过程的重要部分。同源性分析和进化树显示灵长类动物与人类ACE2蛋白相似性最高。结论:利用生物信息学方法研究人源ACE2基因和蛋白的基本结构、性质、功能,为新型冠状病毒患者出现的症状机理提供一定的理论支持,对进一步探索疾病发生机制和药物研发提供参考。
基金supported by the National Natural Science Foundation of China(No.81460077,81160041)the Provincial Governor’s Special Fund for Excellent Scientific and Technological Education Talents in Guizhou Province,China [Guizhou Special Character(2012)15]
基金The study was supported by a grant from the National Natural Science Foundation of China (No. 81100160). Conflict of interest: none declared.
文摘Background Growing epidemiologic evidence has indicated that genetics can predispose individuals to the occurrence of lone atrial fibrillation (AF). The angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with hypertension and left ventricular hypertrophy. The objective of our study was to investigate the association of ACE2 gene polymorphisms with lone AF. Methods A total of 265 consecutive lone AF patients and 289 healthy controls were successfully investigated. The polymorphisms rs2106809 and rs2285666 were genotyped by polymerase chain reaction (PCR) and direct sequencing. A Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CO of variations of ACE2 for lone AF. Results The T allele of rs2106809 conferred an increased risk for lone AF (OR 1.24, 95% CI 1.01-1.52, P=0.03) in males after adjustment for conventional risk factors. SNP at rs2285666 in males was not significantly different between AF patients and controls. No association was found between the two polymorphisms in the female population with lone AF. After (36.3±4.5) months of follow-up, the end point data were obtained: death (cardiac and noncardiac), ischemic stroke, and heart failure. In the male subgroup, the associations between rs2106809 T male carriers and combined end points including ischemic stroke, heart failure, and death in our study were of significance (OR 3.6, 95% CI 1.0-13.1, P=-0.04). Conclusions The results indicate that polymorphism at ACE2 gene is associated with male lone AF in a Chinese Han population. Lone AF males who c.arrv the. rs2106809T alle.le, are. associate.d with adverse cardiac, e.ve.nts