New data show that the 2019 novel coronavirus (2019-nCoV) causing the Wuhan outbreak may have been hosted by bats initially and could have been transmitted to humans via currently unknown wild animal(s) sold at the Huanan seafood market, according to results of a study published in The Lancet.
Researchers conducted next-generation sequencing of samples of bronchoalveolar lavage fluid and cultured isolates from patients with viral pneumonia who tested negative for respiratory pathogens (N=9). Of these patients, 8 reported a history of visiting the Huanan seafood market before the onset of illness. The whole-genome sequences of 2019-nCoV from 6 samples were generated by a combination of Sanger, Illumina, and Oxford nanopore sequencing. Phylogenetic analyses of the complete genome and major coding regions were completed; on the basis of the genome sequences obtained, a real-time polymerase chain reaction detection assay was developed.
From the samples obtained from these 9 patients, results demonstrated 8 complete genomes sequences, and 2 partial sequences. These sequences were nearly identical across the whole genome, with sequence identity above 99.98%, which indicated a recent emergence into the human population. Researchers conducted a Blastn search of the complete genomes of 2019-nCoV, which revealed that the most closely related viruses available on GenBank were bat-SL-CoVZC45 (sequence identity 87.99%; query coverage 99%) and another SARS-like betacoronavirus of bat origin, bat-SL-CoVZXC21.
Phylogenetic analysis of 2019-nCoV and its closely related reference genomes, as well as representative betacoronaviruses, revealed that the 5 subgenera formed 5 well-supported branches. The phylogeny of RNA-dependent RNA polymerase of 2019-nCoV was found to be distinct from SARS-CoV; this indicated that this strain of the virus is a novel virus of betacoronavirus from the subgenus Sarbecovirus. While the 2019-nCoV was closer to bat-SL-CoVZC45 and bat-SL-CoVZXC21 at the whole-genome level, the receptor-binding domain of 2019-nCoV fell within lineage B and was closer to that of SARS-CoV.
“Clearly, this infection is a major public health concern, particularly as this outbreak coincides with the peak of the Chinese Spring Festival travel rush, during which hundreds of millions of people will travel through China.” the researchers wrote. “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.”
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding [published online January 30, 2020]. The Lancet. doi: 10.1016/S0140-6736(20)30251-8