The possible origins of 2019-nCoV Coronavirus

Did COVID-19 actually originate from bats? What does the research say?

First thing first, SARS-CoV-2 did not emerge through laboratory manipulation of another coronavirus to be used as a bioweapon. So, where did the demon responsible for COVID-19 originate? We don’t know for sure. But researchers propose two scenarios of its origin:

(i) natural selection in an animal host before the zoonotic transfer
(ii) natural selection in humans following the zoonotic transfer.

1. Given the ~96% similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor (source or ancestor), but can’t efficiently infect humans as-it-is because of different molecular pathways. Since the diversity of coronaviruses in bats and other species is massively undersampled, it is not possible to convincingly tell high-density mutations of the virus within the bat community lead to this. However, the similarity of human coronavirus with Malayan pangolins coronaviruses suggests it could actually be natural selection within the animal community. There is a possibility of intermediate transmissions from bats to humans that we still don’t know.

2. Another possibility is that a progenitor of SARS-CoV-2 jumped into humans, acquiring the right genetic structure through adaptation during undetected human-to-human transmission. Which means, the virus infection already existed for some time. Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases we are detecting now. Studies so far suggest all SARS-CoV-2 may have a common ancestor. This could be a result of a repeated transfer of coronaviruses from bats to humans over a significant period of time that may have lead to this adaptation.

Basic research involving the passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in laboratories across the world and there are documented instances of laboratory escapes of SARS-CoV. In theory, it is possible that SARS-CoV-2 acquired mutations during adaptation to the passage in cell culture. A hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity and many impractical scenarios of human-like transfers to induce those adaptations in laboratories. The finding of nearly identical SARS-CoV-like coronaviruses from pangolins, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutations naturally.

In February 2020, Botao Xiao and Lei Xiao published an investigatory work suggesting an alternative pathway, that is now retracted by China, that is as follows.

The 2019-nCoV coronavirus has caused an epidemic of 28,060 laboratory-confirmed infections in human including 564 deaths in China by February 6, 2020. Two descriptions of the virus published on Nature this week indicated that the genome sequences from patients were 96% or 89% identical to the Bat CoV ZC45 coronavirus originally found in Rhinolophus affinis. It was critical to study where the pathogen came from and how it passed onto human.

An article published on The Lancet reported that 41 people in Wuhan were found to have the acute respiratory syndrome and 27 of them had contact with Huanan Seafood Market. The 2019-nCoV was found in 33 out of 585 samples collected in the market after the outbreak. The market was suspicious to be the origin of the epidemic, and was shut down according to the rule of quarantine the source during an epidemic.

The bats carrying CoV ZC45 were originally found in Yunnan or Zhejiang province, both of which were more than 900 kilometers away from the seafood market. Bats were normally found to live in caves and trees. But the seafood market is in a densely-populated district of Wuhan, a metropolitan of ~15 million people. The probability was very low for the bats to fly to the market. According to municipal reports and the testimonies of 31 residents and 28 visitors, the bat was never a food source in the city, and no bat was traded in the market. There was possible natural recombination or intermediate host of the coronavirus, yet little proof has been reported.

Figure 1. The Huanan Seafood Market is close to the WHCDC (from Baidu and Google maps).

Was there any other possible pathway? We screened the area around the seafood market and identified two laboratories conducting research on bat coronavirus. Within ~280 meters from the market, there was the Wuhan Center for Disease Control & Prevention (WHCDC) (Figure 1). WHCDC hosted animals in laboratories for research purpose, one of which was specialized in pathogens collection and identification. In one of their studies, 155 bats including Rhinolophus affinis were captured in Hubei province, and other 450 bats were captured in Zhejiang province. The expert in collection was noted in the Author Contributions (JHT). Moreover, he was broadcasted for collecting viruses on nation-wide newspapers and websites in 2017 and 2019. He described that he was once by attacked by bats and the blood of a bat shot on his skin. He knew the extreme danger of the infection so he quarantined himself for 14 days. In another accident, he quarantined himself again because bats peed on him. He was once thrilled for capturing a bat carrying a live tick.

Surgery was performed on the caged animals and the tissue samples were collected for DNA and RNA extraction and sequencing. The tissue samples and contaminated trashes were source of pathogens. They were only ~280 meters from the seafood market. The WHCDC was also adjacent to the Union Hospital (Figure 1) where the first group of doctors were infected during this epidemic. It is plausible that the virus leaked around and some of them contaminated the initial patients in this epidemic, though solid proofs are needed in future study. The second laboratory was ~12 kilometers from the seafood market and belonged to Wuhan Institute of Virology, Chinese Academy of Sciences. This laboratory reported that the Chinese horseshoe bats were natural reservoirs for the severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the 2002-3 pandemic. The principle investigator participated in a project which generated a chimeric virus using the SARS-CoV reverse genetics system, and reported the potential for human emergence. A direct speculation was that SARS-CoV or its derivative might leak from the laboratory.

In summary, somebody was entangled with the evolution of 2019-nCoV coronavirus. In addition to origins of natural recombination and intermediate host, the killer coronavirus probably originated from a laboratory in Wuhan. Safety level may need to be reinforced in high risk biohazardous laboratories. Regulations may be taken to relocate these laboratories far away from city center and other densely populated places


References

  1. Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020. https://doi.org/10.1038/s41586-020-2012-7.
  2. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020. https://doi.org/10.1038/s41586-020-2008-3.
  3. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2019. https://doi.org/10.1016/S0140-6736(20)30183-5.
  4. Guo WP, Lin XD, Wang W, et al. Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents. PLoS pathogens 2013; 9(2): e1003159.
  5. Lu M, Tian JH, Yu B, Guo WP, Holmes EC, Zhang YZ. Extensive diversity of rickettsiales bacteria in ticks from Wuhan, China. Ticks and tick-borne diseases 2017; 8(4): 574-80.
  6. Shi M, Lin XD, Chen X, et al. The evolutionary history of vertebrate RNA viruses. Nature 2018; 556(7700): 197-202.
  7. Tao P. Expert in Wuhan collected ten thousands animals: capture bats in mountain at night. Changjiang Times 2017.
  8. Li QX, Zhanyao. Playing with elephant dung, fishing for sea bottom mud: the work that will change China’s future. Thepaper 2019.
  9. Ge XY, Li JL, Yang XL, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013; 503(7477): 535-8.
  10. Menachery VD, Yount BL, Jr., Debbink K, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature medicine 2015; 21(12): 1508-13.

All the rights of above publication are held by Botao Xiao (Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China and School of Physics, Huazhong University of Science and Technology, Wuhan, China) and Lei Xiao (Tian You Hospital, Wuhan University of Science and Technology, Wuhan, China)

Source: https://web.archive.org/web/20200214144447/https://www.researchgate.net/publication/339070128_The_possible_origins_of_2019-nCoV_coronavirus


Sharing the work of Botao Xiao and Lei Xiao doesn’t mean I endorse their views. However, since it is retracted from other platforms, the work should stay in public domain for discussions.

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