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      Phylogenomic proximity and comparative proteomic analysis of SARS-CoV-2

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          Abstract

          The coronavirus disease (COVID-19) belongs to the family Severe Acute Respiratory Syndrome (SARS-CoV). It can be more severe for some persons and can lead to pneumonia or breathing difficulties resulting in the death of immune-compromised patients. We performed a phylogenomic and phylogeographic tree from the collected datasets. Phylogenomic analysis or sequence-based phylogeny showed an evolutionary relationship between the geographical strains. The phylogenomic tree grouped into two major clades consists of various isolates of SARS-CoV-2 and Bat SARS-like coronavirus, Bat coronavirus, and Pangolin coronavirus. The phylogenetic neighbor of newly sequenced Indian strains (Accession: MT012098.1, MT050493.1) was revealed to identify the variations between the nCoV-19 strains. The results showed keen evidence that SARS-CoV-2 has evolved from Bat SARS-like coronavirus. The evolutionary history and comparative proteomic analysis provide a new avenue for the current scientific research related to the coronavirus.

          Highlights

          • The phylogenomic proximity and comparative proteomic study were revealed between Wuhan-Hu-1 and two new Indian isolates of SARS-CoV-2 genomes.

          • SARS-CoV-2 genome has been expanded in human hosts due to the establishment of a hyper-variable genomic hotspot population.

          • At most 30% of proteomic sequence from Wuhan-Hu-1 doesn’t match with Indian isolates and it may offer new ancestry relationships within the subgenus of sarbecovirus.

          • The estimation of amino acid frequencies reveals 9.11 % of leucine-rich repeats were found within the SARS-CoV-2 genomes.

          • The increase of leucine-rich repeats leads to the occurrence of recombinant events within the SARS-CoV-2 genomes.

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          Most cited references13

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

            Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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              Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

              ABSTRACT A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
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                Author and article information

                Contributors
                Journal
                Gene Rep
                Gene Rep
                Gene Reports
                Published by Elsevier Inc.
                2452-0144
                8 July 2020
                8 July 2020
                : 100777
                Affiliations
                [a ]Department of Microbiology, Pondicherry University, Puducherry 605014, India
                [b ]Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India
                Author notes
                [* ]Corresponding author. jselvin.mib@ 123456pondiuni.edu.in
                Article
                S2452-0144(20)30191-6 100777
                10.1016/j.genrep.2020.100777
                7341045
                d38af404-a6dd-4062-ac98-07c62e9a3949
                © 2020 Published by Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 5 June 2020
                : 16 June 2020
                : 6 July 2020
                Categories
                Article

                sars-cov-2,bat sars-cov,coronavirus,bat-cov,pangolin-cov,evolutionary imprints,genetic diversity

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