《BioRxiv,1月30日,2019-nCov的进化和变异》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangzx
  • 发布时间:2020-01-31
  • Background: The current outbreak caused by novel coronavirus (2019-nCoV) in China has become a worldwide concern. As of 28 January 2020, there were 4631 confirmed cases and 106 deaths, and 11 countries or regions were affected. Methods: We downloaded the genomes of 2019-nCoVs and similar isolates from the Global Initiative on Sharing Avian Influenza Database (GISAID and nucleotide database of the National Center for Biotechnology Information (NCBI). Lasergene 7.0 and MEGA 6.0 softwares were used to calculate genetic distances of the sequences, to construct phylogenetic trees, and to align amino acid sequences. Bayesian coalescent phylogenetic analysis, implemented in the BEAST software package, was used to calculate the molecular clock related characteristics such as the nucleotide substitution rate and the most recent common ancestor (tMRCA) of 2019-nCoVs. Results: An isolate numbered EPI_ISL_403928 showed different phylogenetic trees and genetic distances of the whole length genome, the coding sequences (CDS) of ployprotein (P), spike protein (S), and nucleoprotein (N) from other 2019-nCoVs. There are 22, 4, 2 variations in P, S, and N at the level of amino acid residues. The nucleotide substitution rates from high to low are 1.05 × 10-2 (nucleotide substitutions/site/year, with 95% HPD interval being 6.27 × 10-4 to 2.72 × 10-2) for N, 5.34 × 10-3 (5.10 × 10-4, 1.28 × 10-2) for S, 1.69 × 10-3 (3.94 × 10-4, 3.60 × 10-3) for P, 1.65 × 10-3 (4.47 × 10-4, 3.24 × 10-3) for the whole genome, respectively. At this nucleotide substitution rate, the most recent common ancestor (tMRCA) of 2019-nCoVs appeared about 0.253-0.594 year before the epidemic. Conclusion: Our analysis suggests that at least two different viral strains of 2019-nCoV are involved in this outbreak that might occur a few months earlier before it was officially reported.

  • 原文来源:https://www.biorxiv.org/content/10.1101/2020.01.30.926477v1
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  • 《BioRxiv,1月30日,2019-nCoV跨物种进化的见解和疫苗开发中免疫决定因素的定义》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangzx
    • 发布时间:2020-01-31
    • Novel Coronavirus (nCoV) outbreak in the city of Wuhan, China during December 2019, has now spread to various countries across the globe triggering a heightened containment effort. This human pathogen is a member of betacoronavirus genus carrying 30 kilobase of single positive-sense RNA genome. Understanding the evolution, zoonotic transmission, and source of this novel virus would help accelerating containment and prevention efforts. The present study reported detailed analysis of 2019-nCoV genome evolution and potential candidate peptides for vaccine development. This nCoV genotype might have been evolved from a bat-CoV by accumulating non-synonymous mutations, indels, and recombination events. Structural proteins Spike (S), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein contains a 39 nucleotide (5-prime aAT GGT GTT GAA GGT TTT AAT TGT TAC TTT CCT TTA CAA Tca 3-prime) sequence insertion, which shares homology to fish genomic sequence of Myripristis murdjan, an abundant fish type in Indo-Pacific Ocean. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region population. These immunodominant epitopes can be incorporated in universal subunit CoV vaccine. Diverse HLA types and variations in the epitope binding affinity may contribute to the wide range of immunopathological outcomes of circulating virus in humans. Our findings emphasize the requirement for continuous surveillance of CoV strains in live animal markets to better understand the viral adaptation to human host and to develop practical solutions to prevent the emergence of novel pathogenic CoV strains.
  • 《1月30日_加州大学研究新型冠状病毒2019-nCoV的跨物种进化,发现潜在疫苗开发的候选肽段》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-02-06
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