SARS-CoV-2 related coronaviruses found in pangolins

Although bats are likely reservoir hosts for SARS-CoV-2, the virus that causes COVID-19, the identity of any intermediate host that might have facilitated transfer to humans is unknown. Researchers say they have discovered coronaviruses related to SARS-CoV-2 in Malayan pangolins (Manis javanica) and it has been suggested that they could be the missing link for SARS-CoV-2 transmission between bats and humans.

Two recent studies of the virus’ genome reached controversial conclusions: namely, that snakes are intermediate hosts of the new virus, and that a key coronavirus protein shares “uncanny similarities” with an HIV-1 protein. Now, a study in the Journal of Proteome Research refutes both ideas and suggests the involvement of pangolins in the evolution of SARS-CoV-2.

Understanding where SARS-CoV-2 came from and how it spreads is important for its control and treatment. Most experts agree that bats are a natural reservoir of SARS-CoV-2, but an intermediate host was needed for it to jump from bats to humans. A recent study that analysed the new virus’ genome suggested snakes as this host, despite the fact that coronaviruses are only known to infect mammals and birds. Meanwhile, an unrelated study compared the sequence of the spike protein –– a key protein responsible for getting the virus into mammalian cells –– of the new coronavirus to that of HIV-1, noting unexpected similarities. Although the authors withdrew this preprint manuscript after scientific criticism, it spawned rumours and conspiracy theories that the new coronavirus could have been engineered in a lab. Yang Zhang and colleagues (University of Michigan) wanted to conduct a more careful and complete analysis of SARS-CoV-2 DNA and protein sequences to resolve these issues.

Compared to the previous studies, the researchers used larger data sets and newer, more accurate bioinformatics methods and databases to analyse the SARS-CoV-2 genome. They found that, in contrast to the claim that four regions of the spike protein were uniquely shared between SARS-CoV-2 and HIV-1, the four sequence segments could be found in other viruses, including bat coronavirus. After uncovering an error in the analysis that suggested snakes as an intermediate host, the team searched DNA and protein sequences isolated from pangolin tissues for ones similar to SARS-CoV-2. The researchers identified protein sequences in sick animals’ lungs that were 91% identical to the human virus’ proteins. Moreover, the receptor binding domain of the spike protein from the pangolin coronavirus had only five amino acid differences from SARS-CoV-2, compared with 19 differences between the human and bat viral proteins. They say this evidence points to the pangolin as the most likely intermediate host for the new coronavirus, but additional intermediate hosts could be possible.

In another study of coronaviruses in pangolins, published in Nature, Tommy Tsan-Yuk Lam (University of Hong Kong) and colleagues report that these animals do harbour coronaviruses related to SARS-CoV-2. However, they say on current data it cannot be excluded that pangolins acquired their SARS-CoV-2 related viruses independently from bats or another animal host, so that their role in the emergence of human SARS-CoV-2 remains unproven. They say, “Although the epidemiology, pathogenicity, interspecies infectivity and transmissibility of coronaviruses in pangolins remains to be studied, the data presented here strongly suggests that handling these animals requires considerable caution, and that their sale in wet markets should be strictly prohibited.”

Articles:

Zhang, C. X., Zheng, W., Huang, X. Q., Bell, E. W., Zhou, X. G., Zhang, Y. (2020). Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1 Journal of Proteome Research, Article ASAP, doi: 10.1021/acs.jproteome.0c00129

Lam, T.T., Shum, M.H., Zhu, H., Tong, Y., Ni, X., Liao, Y., Wei, W., Cheung, W. Y., Li, W., Li, L., Leung, G. M., Holmes, E. C., Hu, Y., Guan, Y. (2020). Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature, doi: 10.1038/s41586-020-2169-0