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.

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

“…[6][7][8] It is clear that 2019-nCoV is another lineage B β-COV and has been postulated that bat is the primary host. 9 Despite only 75% similarity in genetic sequence to SARS-CoV, 9 , 14 2019-nCoV shares many features with SARS-CoV, such as epidemiology, clinical characteristics, and the entry receptor ACE2 and so on. 14 , 15 , 24 , 25 The 2019-nCoV jumps unpredictably, spreads rapidly and has posed severe threat to public health.…”

“…Replicase polyproteins pp1a and pp1ab, which are ORF1a/b would be proteolytic cleaved into 16 non-structural proteins (nsps) which are involved in the transcription and replication of the virus. 9 In addition, the ORF3b encoded a completely novel short protein without an exact function. The new ORF8 likely encodes a secreted protein formed by an alpha-helix, followed by betasheets that contain six strands that have no known functional domain or motif similarly.…”

“…The new ORF8 likely encodes a secreted protein formed by an alpha-helix, followed by betasheets that contain six strands that have no known functional domain or motif similarly. 9 The S gene of the 2019-nCoV has less than 75% sequence identity to those of the two CoVs, bat SARS-like CoVs (SL-CoVZXC21 and ZC45) and human SARS-CoV. 14 Similarly, the spike glycoprotein encoded by the S genes of the 2019-nCoV was longer than that of the SARS-CoV.…”

“…Subsequently, the full genomic sequence from the Shanghai Public Health Clinical Center argued for a bat origin for the 2019-nCoV. 9 From the beginning, clusters of cases of novel CoV infection were reported to be epidemiologically linked to the Huanan Seafood Wholesale Market. 10 Subsequently, the evidence for the human-to-human transmission of 2019-nCoV was further confirmed by the infection of 15 healthcare practitioners after close contact with once infected patient in a Wuhan hospital.…”

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade

“…1A), which also includes the SARS-CoV and bat CoV ZXC21, the latter and CoV ZC45 being the closest to 2019-nCoV. 2019-nCoV shares~76% amino acid sequence identity in the Spike (S)-protein sequence with SARS-CoV and 80% with CoV ZXC21 (Chan et al, 2020). In this article, we focus on a specific furin-like protease recognition pattern present in the vicinity of one of the maturation sites of the S protein ( Fig.…”