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A coronavirus (CoV) was suspected to be the cause of the December 2019 viral pneumonia outbreak in Wuhan, China, given the epidemiologic similarities with the SARS-CoV outbreak of 2002–2003. To isolate and identify the causative agent, Lu and colleagues used next-generation sequencing from bronchoalveolar fluid and throat swabs from nine patients in Wuhan, China. Of the patients, eight had exposure to the Huanan seafood market and one stayed at a nearby hotel. The investigators isolated viral RNA directly from bronchoalveolar fluid or after growth in human airway epithelial cells. They used reverse transcription to obtain DNA, which they sequenced and annotated.
The analyses revealed a close relationship to bat SARS-like coronavirus (SL-CoV), which belongs to the betacoronavirus genus of the coronavirus family. The assembled genomes were more than 99.9% similar, indicating recent emergence and introduction into humans. The researchers determined that 2019-nCoV is in the Sarbecovirus subgenus of betacoronaviruses, clade 2, whereas SARS-CoV is a clade 3 Sarbecovirus. Although the 2019-nCoV was more closely related at the genome level to the bat SL-CoV, its receptor binding domain (RBD) shared more homology with that of the SARS-CoV, a finding also suggested by three-dimensional structure modeling.
Separately, Zhou and colleagues also sequenced and characterized the 2019-nCoV, isolated from five patients seen at the start of the outbreak. The investigators isolated the virus in two cell lines. Sera from 2019-nCoV patients neutralized the virus at a dilution of 1:40-1:80. Horse anti-SARS-CoV serum also neutralized the virus at a dilution of 1:80. Infectivity assays demonstrated that, similar to SARS-CoV, 2019-nCoV uses the angiotensin converting enzyme II for cell entry.
Lu R et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020 Jan 30; [e-pub]. (https://doi.org/10.1016/S0140-6736(20)30251-8)
Zhou P et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020 Feb 3; [e-pub]. (https://doi.org/10.1038/s41586-020-2012-7)
Comment
The bat source of the 2019-nCoV is confirmed by the phylogenetic analysis presented by Lu, but recombination events are thought to have occurred in an intermediate host between bats and humans. The RBDs of SARS-COV and 2019-nCoV have genetic and structural similarities, and the two viruses use the same human receptor. These findings have implications for vaccine and therapeutics development.