Two recent studies concluded that snakes are the intermediate hosts of SARS-CoV-2, a novel coronavirus that causes the COVID-19 disease, and that four insertions in SARS-CoV-2’s spike protein, a key protein responsible for getting the virus into mammalian cells, share a unique similarity to HIV-1. A new study by University of Michigan researchers refutes both ideas and suggests that Malayan pangolins (Manis javanica) are the missing link for SARS-CoV-2 transmission between bats and humans.
This scanning electron microscope image shows SARS-CoV-2 (round magenta objects) emerging from the surface of cells cultured in the lab. The virus shown was isolated from a patient in the U.S. Image credit: NIAID-RML.
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 analyzed the new virus’ genome suggested snakes as the host, despite the fact that coronaviruses are only known to infect mammals and birds.
Meanwhile, another study reported the identification of four unique insertions that were shared only with HIV-1 and were ‘unlikely to be fortuitous in nature.’
Although the authors withdrew their preprint after scientific criticism, it spawned rumors and conspiracy theories that the new coronavirus could have been engineered in a lab.
In the new study, University of Michigan’s Dr. Yang Zhang and colleagues 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 analyze 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 tissues of Malayan pangolins for ones similar to SARS-CoV-2.
The scientists 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.
“This evidence points to the pangolin as the most likely intermediate host for the new coronavirus, but additional intermediate hosts could be possible,” the study authors said.
The study is published in the Journal of Proteome Research.
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Chengxin Zhang et al. 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. J. Proteome Res, published online March 22, 2020; doi: 10.1021/acs.jproteome.0c00129
