NGS of China coronavirus shows bat origins, intermediate host

By Samantha Black, PhD, The Science Advisory Board staff writer

January 30, 2020 -- Next-generation sequencing (NGS) of 10 genomes of novel coronavirus (2019-nCoV) from nine patients in China demonstrated that the virus is closely related to two coronaviruses that originated in bats, but an intermediate host may be responsible for the spread to humans, according to a study published in Lancet on January 29.

In late December 2019, several patients were identified with viral pneumonia in association with the Huanan seafood market in Wuhan, China. As of January 30, China has reported over 8,200 suspected cases of 2019n-CoV with 170 fatalities. Understanding the origin of this virus and conducting constant surveillance of its spread is essential to prevent further outbreak and protect public health.

In this epidemiological study, the authors presented data from nine patients in Wuhan. They used next-generation sequencing of bronchoalveolar lavage fluid and cultured isolates to identify 2019-nCoV in all nine patients. As a result, they describe the genomic characterization of 10 genomes of the novel virus, revealing important information about the origin and mechanisms of the virus.

Eight of the nine patients had visited the Huanan seafood market in Wuhan, while one stayed in a nearby hotel before the onset of illness. Human-to-human transmission has been confirmed in family members and medical workers, which is a concern because the peak of infections coincided with the peak of the Chinese spring festival travel rush on January 25.

The researchers conducted phylogenic analysis of 2019-nCoV sequenced from the patients and found that the virus belongs to the subgenus Sarbecovirus. Interestingly, 2019-nCoV is more closely related to two bat-derived coronavirus strains, bat-SL-CoVZC45 and bat-SL-CoVZXC21 (sharing 88% sequence identity), than human-infecting coronaviruses, including the viruses that caused the severe acute respiratory syndrome (SARS) outbreak of 2003 (sharing only 79%) or the Middle East respiratory syndrome (MERS) outbreak in 2013 (sharing about 50%).

Molecular modeling was used to understand receptor binding of 2019-nCoV compared with SARS-CoV and MERS-CoV. The analysis suggested that the receptor-binding domain of 2019-nCoV was composed of a core and an external domain, where the external subdomain is similar to that of SARS-CoV. The structural similarity between SARS-CoV and 2019-nCoV indicates that they may use the same receptor, angiotensin-converting enzyme 2 (ACE2).

The sequences of 2019-nCoV from the different patients were almost identical, with greater than 99.9% sequence identity, suggesting that the virus originated from one source within a very short period. The data suggest that another animal is acting as an intermediate between bats and humans:

  1. The outbreak was first reported in late December 2019, when most bat species in Wuhan are hibernating.
  2. No bats were sold or found at the Huanan seafood market, although other mammals were.
  3. Bat-SL-CoVZC45 and bat-SL-CoVZXC21 are not direct ancestors of 2019-nCoV, given that the sequence identity between them was less than 90%.
  4. In both SARS-CoV and MERS-CoV, bats acted as the natural reservoir with an intermediate host (masked pam civet and dromedary camels, respectively).

The intermediate host, in this case, may be a wild animal sold at the Huanan seafood market.

"It is, therefore, striking that the sequences of 2019-nCoV described here from different patients were almost identical," wrote the authors, led by Roujian Lu of the National Health Commission's Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, and the Chinese Center for Disease Control and Prevention. "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."


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