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

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


From genomic surveillance of clinical samples from patients with viral pneumonia in Wuhan, China, a novel coronavirus (termed 2019-nCoV) has been identified.

Our phylogenetic analysis of 2019-nCoV, sequenced from nine patients’ samples, showed that the virus belongs to the subgenus Sarbecovirus. 2019-nCoV was more similar to two bat-derived coronavirus strains, bat-SL-CoVZC45 and bat-SL-CoVZXC21, than to known human-infecting coronaviruses, including the virus that caused the SARS outbreak of 2003.

Epidemiologically, eight of the nine patients in our study had a history of exposure to the Huanan seafood market in Wuhan, suggesting that they might have been in close contact with the infection source at the market. However, one patient had never visited the market, although he had stayed in a hotel near the market before the onset of their illness. This finding suggests either possible droplet transmission or that the patient was infected by a currently unknown source. Evidence of clusters of infected family members and medical workers has now confirmed the presence of human-to-human transmission. 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.
As a typical RNA virus, the average evolutionary rate for coronaviruses is roughly 10−4 nucleotide substitutions per site per year, with mutations arising during every replication cycle. It is, therefore, striking that the sequences of 2019-nCoV from different patients described here were almost identical, with greater than 99·9% sequence identity. This finding suggests that 2019-nCoV originated from one source within a very short period and was detected relatively rapidly. However, as the virus transmits to more individuals, constant surveillance of mutations arising is needed.
Phylogenetic analysis showed that bat-derived coronaviruses fell within all five subgenera of the genus Betacoronavirus. Moreover, bat-derived coronaviruses fell in basal positions in the subgenus Sarbecovirus, with 2019-nCoV most closely related to bat-SL-CoVZC45 and bat-SL-CoVZXC21, which were also sampled from bats. These data are consistent with a bat reservoir for coronaviruses in general and for 2019-nCoV in particular. However, despite the importance of bats, several facts suggest that another animal is acting as an intermediate host between bats and humans. First, the outbreak was first reported in late December, 2019, when most bat species in Wuhan are hibernating. Second, no bats were sold or found at the Huanan seafood market, whereas various non-aquatic animals (including mammals) were available for purchase. Third, the sequence identity between 2019-nCoV and its close relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21 was less than 90%, which is reflected in the relatively long branch between them. Hence, bat-SL-CoVZC45 and bat-SL-CoVZXC21 are not direct ancestors of 2019-nCoV. Fourth, in both SARS-CoV and MERS-CoV, bats acted as the natural reservoir, with another animal (masked palm civet for SARS-Co and dromedary camels for MERS-CoV) acting as an intermediate host, with humans as terminal hosts. Therefore, on the basis of current data, it seems likely that the 2019-nCoV causing the Wuhan outbreak might also be initially hosted by bats, and might have been transmitted to humans via currently unknown wild animal(s) sold at the Huanan seafood market.
Previous studies have uncovered several receptors that different coronaviruses bind to, such as ACE2 for SARS-CoV and CD26 for MERS-CoV.
Our molecular modelling showed structural similarity between the receptor-binding domains of SARS-CoV and 2019-nCoV. Therefore, we suggest that 2019-nCoV might use ACE2 as the receptor, despite the presence of amino acid mutations in the 2019-nCoV receptor-binding domain. Although a previous study using HeLa cells expressing ACE2 proteins showed that 2019-nCoV could employ the ACE2 receptor, whether these mutations affect ACE2 binding or change receptor tropism requires further study.
Recombination has been seen frequently in coronaviruses.
As expected, we detected recombination in the Sarbecoviruses analysed here. Our results suggest that recombination events are complex and are more likely occurring in bat coronaviruses than in 2019-nCoV. Hence, despite its occurrence, recombination is probably not the reason for emergence of this virus, although this inference might change if more closely related animal viruses are identified.
In conclusion, we have described the genomic structure of a seventh human coronavirus that can cause severe pneumonia and have shed light on its origin and receptor-binding properties. More generally, the disease outbreak linked to 2019-nCoV again highlights the hidden virus reservoir in wild animals and their potential to occasionally spill over into human populations.
GFG, WT, WS, WC, WX, and GW designed the study. RL, XZ, PN, HW, WW, BH, NZ, XM, WZ, LZ, JC, YM, JW, YL, JY, ZX, JM, WJL, and DW did the experiments. BY, FZ, and ZH provided samples. WS, WC, WT, JL, HS, YB, LW, TH, and HZ analysed data. WS, WT, and JL wrote the report. ECH and GFG revised the report.

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding  The LancetView full coverage on Google News
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding – The Lancet

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