Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

TLDR

A mysterious outbreak of atypical pneumonia in late 2019 in Wuhan led to the identification of a novel coronavirus, 2019‑nCoV, by the WHO. The study aims to identify the animal source of 2019‑nCoV to elucidate its origin and evolution. The authors performed comparative genomic analysis of a patient‑derived 2019‑nCoV genome against related coronaviruses. The 2019‑nCoV genome shares 89 % identity with bat SARS‑like‑CoVZXC21 and 82 % with human SARS‑CoV, clusters phylogenetically with SARS coronaviruses, but its Spike receptor‑binding domain shows only 40 % amino‑acid identity, and it encodes novel proteins (orf3b and orf8) that may inform pathogenesis and guide diagnostic, antiviral, and vaccine development.

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.