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  Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development
  Authors: Arunachalam Ramaiah; Vaithilingaraja Arumugaswami
  doi:10.1101/2020.01.29.925867 Date: 2020-01-30 Source: bioRxiv
  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 MESHD proteins Spike (S PROTEIN), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins PROTEIN were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein PROTEIN contains a 39 nucleotide sequence insertion relative to SARS-like bat-SL-CoVZC45/2017. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins PROTEIN, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region MESHD 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.
  Authors: Chenglong Xiong; Lufang Jiang; Yue Chen; Qingwu Jiang
  doi:10.1101/2020.01.30.926477 Date: 2020-01-30 Source: bioRxiv
  BackgroundThe 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. MethodsWe 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. ResultsAn 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 PROTEIN), and nucleoprotein (N PROTEIN) 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{middle dot}05 x 10-2 (nucleotide substitutions/site/year, with 95% HPD interval being 6.27 x 10-4 to 2.72 x 10-2) for N, 5.34 x 10-3 (5.10 x 10-4, 1.28 x 10-2) for S, 1.69 x 10-3 (3.94 x 10-4, 3.60 x 10-3) for P, 1.65 x 10-3 (4.47 x 10-4, 3.24 x 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. ConclusionOur 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.
  Authors: Tao Liu; Jianxiong Hu; Jianpeng Xiao; Guanhao He; Min Kang; Zuhua Rong; Lifeng Lin; Haojie Zhong; Qiong Huang; Aiping Deng; Weilin Zeng; Xiaohua Tan; Siqing Zeng; Zhihua Zhu; Jiansen Li; Dexin Gong; Donghua Wan; Shaowei Chen; Lingchuan Guo; Yan Li; Limei Sun; Wenjia Liang; Tie Song; Jianfeng He; Wenjun Ma
  doi:10.1101/2020.01.25.919787 Date: 2020-01-26 Source: bioRxiv
  RationaleSeveral studies have estimated basic production number of novel coronavirus pneumonia MESHD ( NCP PROTEIN). However, the time-varying transmission dynamics of NCP PROTEIN during the outbreak remain unclear. ObjectivesWe aimed to estimate the basic and time-varying transmission dynamics of NCP PROTEIN across China, and compared them with SARS. MethodsData on NCP PROTEIN cases by February 7, 2020 were collected from epidemiological investigations or official websites. Data on severe acute respiratory syndrome (SARS) cases in Guangdong Province, Beijing and Hong Kong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of NCP PROTEIN and SARS. Measurements and main resultsAs of February 7, 2020, 34,598 NCP PROTEIN cases were identified in China, and daily confirmed cases decreased after February 4. The doubling time of NCP PROTEIN nationwide was 2.4 days which was shorter than that of SARS in Guangdong (14.3 days), Hong Kong (5.7 days) and Beijing (12.4 days). The R0 of NCP PROTEIN cases nationwide and in Wuhan were 4.5 and 4.4 respectively, which were higher than R0 of SARS in Guangdong (R0=2.3), Hongkong (R0=2.3), and Beijing (R0=2.6). The Rt for NCP PROTEIN continuously decreased especially after January 16 nationwide and in Wuhan. The R0 for secondary NCP PROTEIN cases in Guangdong was 0.6, and the Rt values were less than 1 during the epidemic. ConclusionsNCP may have a higher transmissibility than SARS, and the efforts of containing the outbreak are effective. However, the efforts are needed to persist in for reducing time-varying reproduction number below one. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSSince December 29, 2019, pneumonia infection with 2019-nCoV, now named as Novel Coronavirus Pneumonia ( NCP PROTEIN), occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other areas. As a novel virus, the time-varying transmission dynamics of NCP PROTEIN remain unclear, and it is also important to compare it with SARS. What This Study Adds to the FieldWe compared the transmission dynamics of NCP PROTEIN with SARS, and found that NCP PROTEIN has a higher transmissibility than SARS. Time-varying production number indicates that rigorous control measures taken by governments are effective across China, and persistent efforts are needed to be taken for reducing instantaneous reproduction number below one.
  Authors: Domenico Benvenuto; Marta Giovanetti; Alessandra Ciccozzi; Silvia Spoto; Silvia Angeletti; Massimo Ciccozzi
  doi:10.1101/2020.01.24.915157 Date: 2020-01-24 Source: bioRxiv
  There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein PROTEIN has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins PROTEIN. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.