Current Location:home > Browse

Submitted Date

1. chinaXiv:202002.00071 [pdf]

Potential treatment of Chinese and Western Medicine targeting nsp14 of 2019 nCov

Liu Chao ; Zhu Xiaoxiao ; Lu Yiyao ; Jia Xu ; Yang Tai
Subjects: Medicine, Pharmacy >> Pharmacology

2019年12月,自武汉开始我国爆发严重的新型冠状病毒(2019-nCoV)感染疫情,急需开发2019-nCoV治疗药物。冠状病毒非结构蛋白 (Nonstructural protein, NSP) 在病毒基因组复制以及转录过程中起重要作用,在冠状病毒家族中普遍保守,是冠状病毒重要功能蛋白。其中,NSP14蛋白兼具核酸外切酶和甲基转移酶功能,是抗SARS和其他冠状病毒药物研究的重要靶点。序列分析表明, SARS coronavirus (PDB ID: 5nfy) 与武汉华南海鲜批发市场新型冠状病毒分离毒株 (GenBank: MN985325.1)氨基酸序列同源性为98.7%。本研究通过已发表的SARS-NSP14晶体结构 (PDB ID: 5nfy) 进行同源建模,构建2019-nCoV-NSP14的蛋白三维结构模型,对其N端-甲基转移酶以及C端-甲基转移酶结构功能域分别进行虚拟筛选,筛选出了18个对NSP14有抑制活性的化合物。其中沙奎那韦 (Saquinavir)、溴隐亭 (Bromocriptine)、黄芩苷 (Baicalein) 以及金丝桃素 (Hypericin) 能同时作用于NSP14蛋白上述两个重要功能域。该结果提示已知抗HIV药物-Saquinavir以及中药抗病毒重要活性成分-黄芩苷以及金丝桃素,可能以2019-nCoV-NSP14蛋白为靶标,发挥抗病毒效应,可作为抗2019-nCov候选药物进行下一步研究。

submitted time 2020-02-27 Hits19290Downloads1363 Comment 0

2. chinaXiv:202002.00070 [pdf]

Towards an effective mRNA vaccine against 2019-nCoV: demonstration of virus-like particles expressed from a modified mRNA cocktail

Xia, Jia; Lu, Guoliang; Lu, Jing; Zhang, Jiahui; Feng, Lin; Wang, Bing; Yu, Hang; Xu, Yingjie; Lin, Jinzhong
Subjects: Biology >> Virology

Frequent outbreaks of coronavirus make the development of an effective vaccine imperative. Recently, vaccines based on in-vitro transcribed messenger RNA (mRNA) have shown great potential. The streamlined manufacturing of mRNA molecules, combined with the superior flexibility in the antigen screening, greatly accelerates the development process. When using an mRNA platform to develop a vaccine, initial antigen choice plays a crucial role in determining the final efficacy and safety of the vaccine. Furthermore, mRNA sequences that encode antigens require extensive optimization to ensure highly efficient and sustained expression. Our ongoing efforts to develop an effective mRNA vaccine against 2019-nCoV place emphasis on the virus-like particles (VLPs) as the presenting antigen. At the same time, our second fast track uses mRNA to express the receptor-binding domain of the spike protein(S-RBD). After extensive optimization, an mRNA cocktail containing three genes is able to produce 2019-nCoV virus-like particles highly similar to the native 2019-nCoV. Meanwhile, an mRNA vaccine candidate expressing S-RBD is being tested in mice for its immunogenicity. We will next compare both the efficacy and the safety of the two mRNA vaccines based on S-RBD and VLPs, respectively.

submitted time 2020-02-25 Hits10422Downloads1476 Comment 0

3. chinaXiv:202002.00033 [pdf]

Decoding evolution and transmissions of novel pneumonia coronavirus using the whole genomic data

Yu, Wen-Bin; Tang, Guang-Da; Zhang, Li; Corlett, Richard T.
Subjects: Biology >> Virology
Subjects: Biology >> Genetics

Background. The outbreak of COVID-19 started in mid-December 2019 in Wuhan, Central China. Up to February 18, 2020, SARS-CoV-2 has infected more than 70,000 people in China, and another 25 countries across five continents. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to decode the evolution and human-to-human transmissions of SARS-CoV-2 in the recent two months. Methods. Alignment of coding-regions was conducted haplotype analyses using DnaSP. Substitution sites were analyzed in codon. Evolutionary analysis of haplotypes used NETWORK. Population size changes were estimated using both DnaSP and Arlequin. Expansion date of population size was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. Findings. Eight coding-regions have 120 substitution sites, including 79 non-synonymous and 40 synonymous substitutions. Forty-two non-synonymous substitutions changed the biochemical property of amino acids. No evident combination was found. Fifty-eight haplotypes were classified as five groups, and 31 haplotypes were found in samples from both China and other countries, respectively. The rooted network suggested H13 and H35 to be ancestral haplotypes, and H1 (and its descendent haplotypes including all samples from the Hua Nan market) was derived H3 haplotype. Population size of SARS-CoV-2 were estimated to have a recent expansion on 6 January 2020, and an early expansion on 8 December 2019. Interpretation. Genomic variations of SARS-CoV-2 are still low in comparisons with published genomes of SARS-CoV and MERS-CoV. Phyloepidemiologic analyses indicated the SARS-CoV-2 source at the Hua Nan market should be imported from other places. The crowded market boosted SARS-CoV-2 rapid circulations in the market and spread it to the whole city in early December 2019. Furthermore, phyloepidemiologic approaches have recovered specific direction of human-to-human transmissions, and the import sources of international infectious cases.

submitted time 2020-02-21 Hits284596Downloads72231 Comment 0

4. chinaXiv:202002.00034 [pdf]

病毒核酸提取前的高温灭活过程显著降低可检出病毒核酸模板量

张沁欣; 赵庆顺
Subjects: Biology >> Molecular Biology

新冠病毒是病毒感染性肺炎(COVID-19)的病原体。然而,新冠病毒核酸临床检出的假阴性率很高。假阴性意味着漏检,不仅会导致疑似患者不能快速确诊,而且会使漏检者成为潜在的病毒传染源。因此,提高新冠病毒核酸检出率十分迫切。目前国家卫健委相关指南要求在提取样本核酸前需将样本置于56℃以上以灭活病毒。这一灭活过程无疑是保护临检人员免受病毒暴露所必需,但也会破坏病毒核酸的完整性,导致部分样品不能被正常检出,成为高假阴性率的原因之一。最近,我们以猪PDEV冠状病毒(疫苗)作为模型研究了高温灭活过程对病毒核酸完整性的影响。结果表明:保存在常用等渗盐溶液Hank’s液中的样品经56℃孵育30分钟后可检出冠状病毒核酸损坏了一半,而以92℃孵育5分钟,则可检出的冠状病毒核酸损失了96%以上。当采用一款市售的R503样品保存液保存PEDV时,经56℃孵育30分钟后病毒核酸可检出量是Hank’s液的3倍,若是92℃孵育5分钟,则可检出量是Hank’s液的42倍。这些结果提示,使用可有效保护样本RNA特别是避免样本RNA在高温灭活时受损的样品保存液,不但可以让临检人员依然能够在高温灭活后使用样品,还有望提高阳性检出率。

submitted time 2020-02-20 Hits10631Downloads2013 Comment 0

5. chinaXiv:202002.00028 [pdf]

新型冠状病毒(2019-nCoV)时空数据集及其典型应用

林浩; 鲍君雅
Subjects: Survey & Drawing Science and Technology >> Photogrammetry and Remote Sensing
Subjects: Statistics >> Biomedical Statistics

目前,新型冠状病毒(2019-nCoV)疫情正受到全球各科研工作者的广泛关注。然而,当前尚没有一个官方的渠道对2019-nCoV疫情数据进行实时开源,为了促进本次疫情相关的科研工作,本研究旨在为广大科研工作者提供权威的、开放的和多尺度的新型冠状病毒(2019-nCoV)时空数据集,为疫情监测、防控、预测和预警提供重要的数据来源。此外,该数据集还能应用于2019-nCoV疫情的多尺度、多时相制图和可视化,为疫情的空间分布、演化、趋势分析和模拟预测提供指导。

submitted time 2020-02-19 Hits20474Downloads1703 Comment 0

6. chinaXiv:202002.00028 [pdf]

新型冠状病毒(2019-nCoV)时空数据集及其典型应用

林浩; 鲍君雅
Subjects: Survey & Drawing Science and Technology >> Photogrammetry and Remote Sensing
Subjects: Statistics >> Biomedical Statistics

目前,新型冠状病毒(2019-nCoV)疫情正受到全球各科研工作者的广泛关注。然而,当前尚没有一个官方的渠道对2019-nCoV疫情数据进行实时开源,为了促进本次疫情相关的科研工作,本研究旨在为广大科研工作者提供权威的、开放的和多尺度的新型冠状病毒(2019-nCoV)时空数据集,为疫情监测、防控、预测和预警提供重要的数据来源。此外,该数据集还能应用于2019-nCoV疫情的多尺度、多时相制图和可视化,为疫情的空间分布、演化、趋势分析和模拟预测提供指导。

submitted time 2020-02-17 Hits201Downloads130 Comment 0

7. chinaXiv:202002.00015 [pdf]

人工智能在新型冠状病毒(2019-nCoV)肺炎的应用进展:需求和机遇

王永桂; 李强; 余晴; 杨水化; 徐子怡; 谢天奕; 胡珊
Subjects: Computer Science >> Computer Application Technology

[目的]探究人工智能在新型冠状病毒(2019-nCoV)的诊断、治疗和控制中的应用场景和进展,以利用人工智能为新型冠状病毒肺炎的防控提供助力。 [方法]剖析新型冠状病毒肺炎防控的技术需求,从人工智能基因测序、辅助诊断、远程专家系统、药物筛查与研制等方面,分析当前的应用进展,挖掘应用的机遇。 [结果]中国是新型冠状病毒疫情最严重的国家,存在诸多的技术短板有待科技助力,AI能在疫情防控中发挥出重要的作用,但目前处于初步阶段,缺乏经过验证的落地成果;AI辅助诊断领域重复性研发较多,其他方面研究较少。 [局限]当前应用的数据大部分来自网站报道,如有更多的学术性成果,进展的分析将更全面。 [结论]需要加大投入和调控,在数据、算法和算力共享的基础上,各方面全面展开研发。

submitted time 2020-02-15 Hits22090Downloads1339 Comment 0

8. chinaXiv:202002.00018 [pdf]

2019-novel coronavirus (2019-nCoV) infections trigger an exaggerated cytokine response aggravating lung injury

Yingxia Liu; Cong Zhang; Fengming Huang; Yang Yang; Fuxiang Wang; Jing Yuan; Zheng Zhang; Yuhao Qin; Xiaoyun Li; Dandan Zhao; Shunwang Li; Shuguang Tan; Zhaoqin Wang; Jinxiu Li; Chenguang Shen; Jianming Li; Ling Peng; Weibo Wu; Mengli Cao; Li Xing
Subjects: Biology >> Biochemistry

最近,在中国武汉爆发了肺炎病例,由一种名为2019-CoV的新型冠状病毒引起。我们之前的研究中,根据中国深圳的12例2019-nCoV感染患者的临床特征,所有病例均患有肺炎,一半病例发展为急性呼吸窘迫综合征(ARDS)。本文中,我们针对这12例患者的血浆因子表达谱进行了研究。我们测试了2019-nCoV感染患者血浆中的48个因子的表达,其中38个因子与健康个体相比显着升高;2019-nCoV感染的重症患者血浆中的高细胞因子血症水平显著低于A型流感病毒H7N9感染患者,而略高于细菌感染患者。在这38个细胞因子中,有17个与2019-CoV病毒载量相关,其中的15个(M-CSF,IL-10,IFN-α2,IL-17,IL-4,IP-10,IL-7,IL-1受体拮抗剂,G-CSF,IL-12 (p40),IFN-γ,IL-1α,IL-2,HGF和PDGF-BB)与肺损伤Murray评分高度相关,可用来预测2019-nCoV感染患者的疾病严重程度。我们的研究结果表明,这15种高细胞因子可能是衡量2019-nCoV感染患者疾病严重程度的潜在生物标志物,影响这些信号传递介质的因子可能是针对新型2019-nCoV大流行的潜在药物。

submitted time 2020-02-12 Hits15401Downloads2738 Comment 0

9. chinaXiv:202002.00014 [pdf]

Clinical and Biochemical Indexes from 2019-nCoV infected patients linked to viral loads and lung injury

Yingxia Liu; Yang Yang; Cong Zhang; Fengming Huang; Fuxiang Wang; Jing Yuan; Zhaoqin Wang; Jingxiu Li; Jianming Li; Cheng Feng; Zheng Zhang; Lifei Wang; Ling Peng; Li Chen; Yuhao Qin; Dandan Zhao; Shuguang Tan; Lu Yin; Jun Xu; Congzhao Zhou
Subjects: Biology >> Biochemistry

新型冠状病毒(2019-nCoV)自2019年12月在湖北省武汉市爆发,并迅速传播到中国多地及其他国家。在本研究中,我们报告了来自中国深圳早期的2019-nCoV感染患者的流行病学、临床指标、生化指标和影像学特征,以及可用于预测疾病严重程度的潜在生物标记物。所有12例2019-nCoV感染的肺炎患者均发展为肺炎,其中一半患者进一步发展为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)。最常见的实验室检测生化指标异常是低白蛋白(albumine,ALB)血症、淋巴细胞(lymphocytes,LYM)计数减少,淋巴细胞百分比和中性粒细胞(neutrophils,NEU)百分比降低,C反应蛋白(C-reactive protein,CRP)和乳酸脱氢酶(lactate dehydrogenase,LDH)水平升高,以及CD8细胞计数降低。从患者呼吸道特别是下呼吸道检测到的2019-nCoV病毒滴度与肺部疾病的严重程度正相关。 ALB、LYM、LYM(%)、LDH、NEU(%)和CRP的水平与急性肺损伤程度高度相关。年龄、病毒滴度、肺损伤评分和血液生化指标:ALB、CRP、LDH、LYM(%)、LYM和NEU(%)可能是疾病严重程度的预测指标。此外, 2019-nCoV感染患者的血浆血管紧张素II水平显着升高,并且与病毒滴度和肺损伤程度线性相关。我们的研究结果提供了多种潜在的可用于诊断的生物标志物, 并提出了血管紧张素 II受体阻滞剂(angiotensin II receptor blocker,ARB)药物或可作为治疗2019-nCoV感染的潜在药物进行深入研究。

submitted time 2020-02-08 Hits7621Downloads912 Comment 0

10. chinaXiv:202002.00006 [pdf]

运输,病原微生物,文化:2019-nCoV传播的动态图模型

杨晓飞; 徐暾; 贾鹏; 夏涵; 郭立; 叶凯
Subjects: Computer Science >> Computer Application Technology

自从武汉市爆发新型冠状病毒疫情以来,迅速蔓延的事态已经造成300多人死亡,一万多人感染。在中国之外有一百多起病例,影响了全球十几个国家。研究人员已经报道了冠状病毒的全基因组序列,并且正在迅速开发快速诊断试剂盒、有效的治疗方法以及预防性疫苗。最初快速增长的确诊病例触发了武汉及附近城市的封锁。世界各地的科学家尝试建立数学模型来预测未来几天内的感染病例数。但是,交通和文化习俗等主要因素尚未得到足够的权衡。我们的模型并不是为了精确预测感染病例数量,而是旨在模拟公共流行紧急情况下的动态情况以及不同影响因素的贡献。我们希望我们的模型和模拟能够为全球公共卫生机构提供更多的见解和观点信息,以便设计出更好的预防和控制解决方案。

submitted time 2020-02-03 Hits15762Downloads1220 Comment 0

  [1 Pages/ 10 Totals]