Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Abstract

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. MethodsWe 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 angiotensinconverting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.

2019_nCoV/SARS-CoV-2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses

“…Of these bat species, the first three can be found in the province of Hubei (source: www. This produced the highest identity to the same isolate that Lu and coworkers had identified (Lu et al 2020), demonstrating that an analysis of 253 nucleotides directly upstream of the start codon of the polycystronic messenger suffices to identify genetic relationships between Sarbecovirus species. A number of whole genome Sarbecovirus sequences isolated from these bats and other bat species were selected and their 5'-flank was compared to that of 2019_nCoV (Fig.…”

Coronavirus 2019-nCoV: A brief perspective from the front line

“…12 , 14 The spike protein, composed of S1 and S2 domain, was crucial to the determine host tropism and transmission capacity through the mediation of receptor binding and membrane fusion. 12 Among these, the S2 subunit of the 2019-nCoV is highly conserved and has a 99% identity with that of SARS-CoV. 12 The receptor-binding domain, is commonly located in the C-terminal domain of S1 to directly contact the human receptor.…”

“…12 Among these, the S2 subunit of the 2019-nCoV is highly conserved and has a 99% identity with that of SARS-CoV. 12 The receptor-binding domain, is commonly located in the C-terminal domain of S1 to directly contact the human receptor. Although, the S1 domain of the 2019-nCoV only has approximately 70% identity with SARS-CoV, homology modelling revealed that the 2019-nCoV has a similar receptor-binding domain structure to that of SARS-CoV.…”

Understanding the emerging coronavirus: what it means for health security and infection prevention

“…5 A novel 2019 coronavirus (SARS-CoV-2) belongs to the Betacoronavirus genus of the Coronaviridae family. It shares more than 79% homology with SARS-CoV, 6 and causes mild to severe disease, with fatal bilateral viral pneumonia described in humans. 7 ,8 It is referred to as a novel coronavirus because it has not previously been observed in the human population.…”