Coronavirus Source Potentially Traced to Malayan Pangolins

Since the first cases of infection by the 2019 novel coronavirus (2019-nCoV) were reported in Wuhan, China, in December 2019, the virus has caused over 90,000 cases of the disease COVID-19 around the world with an estimated mortality rate of 3.4%. Currently, the virus has spread across the globe to the United States and, according to the CDC, presumptively infected individuals in Florida, Georgia, New Hampshire, New York, Rhode Island, and Washington among other states.

Since understanding the origins of the 2019-nCoV in greater detail could support the development of better therapies for COVID-19 and more effective measures for preventing the transmission of deadly viruses to humans from other species in the future, research in this sphere is critically important, and over the past month considerable progress has been made. The 2019-nCoV source may be traced to Malayan Pangolins, which could have served as intermediate hosts for a bat-derived virus.

Where did the coronavirus originate?

Following epidemiological investigation, researchers identified that human cases of the virus originated at a seafood market in Wuhan, Hubei Province, China, known to sell live poultry and exotic animals. Genetic analysis demonstrated that the genome of the 2019-nCoV is more similar to that of a bat coronavirus (bat-SL-CoVZC45) than that of the human SARS-CoV, suggesting that the novel coronavirus infecting humans may have originated in bats.

Since bats are known to be a natural reservoir for numerous SARS-related coronaviruses (SARSr-CoVs), some of which have the potential to infect humans, this bat-origin hypothesis of the 2019-nCoV has gained traction and is supported by considerable evidence.

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To shed light on this hypothesis, chinese scientists sequenced the genomes of coronaviruses isolated from humans and bats and discovered that the coronavirus RaTG13, endemic to the horseshoe bat (Rhinolophus), has an overall genome sequence similarity of 96.2% to that of the novel human coronavirus. Since the human SARS-CoV, responsible for an epidemic 18 years ago, was also traced to SARS-like coronaviruses found naturally in horseshoe bats, it seems likely that the 2019-nCoV may have followed in similar footsteps.

While evidence most strongly supports the hypothesis that the 2019-nCoV originated in bats, the transmission events that led to cases of infection among humans remain less clear. The virus is unlikely to have been directly transmitted from bats to humans during December, a period of natural bat hibernation.

How could the coronavirus have been transmitted from bats to humans?

Researchers have proposed that the virus did not transmit directly from bats to humans but rather through an intermediate host such as the Malayan Pangolin. Pangolins, or scaly anteaters, are nocturnal mammals native to Asia and Sub-Saharan Africa that are largely solitary, dine on termites and ants, and are covered by large defensive scales made of keratin.

Unfortunately, pangolins are highly trafficked by poachers. As of January 2020, three of the eight pangolin species were regarded as critically endangered by the International Union for Conservation of Nature Red List of Threatened Species. Pangolins are hunted in southern China for their scales, which are thought to have medicinal properties in Chinese traditional medicine, and for their meat, which is regarded as a delicacy.

Using published data regarding SARS-like coronaviruses isolated from lung samples of deceased Malayan Pangolins, Dr. Tao Zhang and other researchers from Yunnan University identified the occurrence of a virus in pangolins highly similar to the 2019-nCoV (known as Pangolin-CoV), which shares a whole genome similarity of 91.02% and 90.55% to the human 2019-nCoV and bat RaTG13, respectively.

The researchers demonstrated that the Pangolin-CoV is the lowest common ancestor 2019-nCOV and RaTG13, and that the Pangolin-CoV shares key amino acid residues with the human 2019-nCoV at a structural location important for enabling transmission into human cells.

While these residues were consistent between Pangolin-CoV and human 2019-nCoV, they were not shared with the bat coronavirus RaTG13, indicating that the pangolin virus, but not the bat coronavirus, could potentially infect human cells with similar pathogenicity to 2019-nCoV. This phenotype fits logically within the proposed bat-to-pangolin-to-human progression of the virus and, according a recent publication in bioRxiv, suggests that the 2019-nCoV could have resulted from the recombination of a pangolin and a bat coronavirus.

Did the coronavirus come from Pangolins?

Since a whole genome match rate of at least 99.8% is required to definitively ascertain whether the human coronavirus was directly transmitted from pangolins, researchers are still uncertain whether this mode of transmission actually occurred. However, it remains possible, and even reasonable given the widespread nature of illegal pangolin trafficking in China. Indeed, 2019-nCoV was found to have emerged from the Huanan Seafood Wholesale Market in the central Chinese city of Wuhan.

Until its closure in January 2020, the market was regarded as the largest wholesale seafood market in central China, and offered exotic and wild animals in addition to seafood. Indeed, pangolins were offered at the market, in addition to hedgehog, crocodiles, koalas, peacocks, wolf puppies, and other animals. While the market passed inspection by city officials in late 2019, it was reported to have “unsanitary” conditions by Time magazine and “dismal [sanitation] with poor ventilation and garbage piled on wet floors” by the New York Times.

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Coronaviruses are known to circulate naturally within pangulins, and viruses similar to the 2019-nCoV have been identified from samples of pangolin tissue. A recent study evaluating frozen tissue samples collected from smuggled Malayan pangolins by the Guangxi Customs between August 2017 and January 2018 identified the presence of 2019-nCoV-related viruses in blood, lung, and intestinal tissue.

There are clinical similarities between coronavirus infection in pangolins and in humans. Histopathological examination of coronavirus-infected pangolins has demonstrated hemorrhaging in the alveolar ducts of the lungs and interstitial pneumonia, traits shared with the disease course of 2019-nCoV.

Other researchers have indicated that, while genetic studies support an association between nCoV-2019 and pangolin coronaviruses, phylogenetic analyses do not provide evidence for the hypothesis that 2019-nCoV arose directly from a pangolin coronavirus.

While the researchers regarded pangolin coronaviruses as genetically similar to the 2019-nCoV and bat coronaviruses, including a high sequence match rate between pangolin coronaviruses and 2019-nCoV, phylogenetic trees assembled using the genomic sequence of the virus indicated the likely involvement of another intermediate host.

The researchers concluded by stating that, while their study did not support the hypothesis that pangolins served as intermediate hosts for the 2019-nCoV, the occurrence of this mode of transmission remains possible given the presence of other pangolin coronaviruses not evaluated within the scope of their study, which could have been the predecessors of 2019-nCoV.

Beyond enhancing our understanding of the origins of the 2019-nCoV, this research has highlighted the critical importance of implementing more effective countermeasures against the illegal trafficking of exotic animals, which is not only morally deplorable but also a potential source of zoonotic transmission of lethal pathogens.

Zhang T, Wu Q, Zhang Z. (2020) Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. CURRENT-BIOLOGY-D-20-00299.

Wu F, Zhao S, Yu B, et al. (2020) A new coronavirus associated with human respiratory disease in China. Nature.

Zhou P, Yang X, Wang X, et al. (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature.

Li X, Song Y, Wong G, and Cui J. (2020). Bat origin of a new human coronavirus: there and back again. Sci China Life Sci, (63). 10.1007/s11427-020-1645-7

Xiao K, Zhai J, Feng Y, et al. (2020) Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins. bioRxiv.

Lam T, Shum M, Zhu H, et al. (2020) Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China. bioRxiv.

Liu P, Jiang J, Wan X, et al. (2020) Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV)? bioRxiv.