Four amino acid insertions (SPRRs) unique to SARS-CoV-2 are marked in yellow. Conserved S1/S2 cleavage sites are marked in green.

Figure 4. CoV S Protein S1/S2 Cleavage
Sites

A putative furin recognition motif, a cleavage site used by furin protease during virus egression, is only found in SARS-CoV-2. This method is similarly used in MERS-CoV. The S protein of Pangolin-CoV and other SARS-like CoV does not have furin sequence motif, demonstrating that SARS-CoV-2 may use a different mechanism for entry into host cells. 

University of Michigan - Ann Arbor

Pangolin is suggested to be an intermediate host of SARS-CoV-2. A study supports this statement using pangolin lung samples detected with SARS-CoV-like CoV (Pangolin-CoV). They found that Pangolin-CoV showed a 90.55% identical genome sequence to RaTG13 (Coronavirus derived from bats) and 91.02% identical genome sequence to SARS-CoV-2. S1 proteins of Pangolin-CoV were also found to be more closely related to SARS-CoV-2 than RaTG13. Both Pangolin-CoV and SARS-CoV-2 also share five key amino acids in the receptor-binding domain (RBD). The results stated above shows that Pangolin-CoV is second closely related to SARS-CoV-2 after bats. 

Pangolin Origin of SARS-CoV-2

Zhang, T., Wu, Q., & Zhang, Z. (2020). Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Current biology : CB, 30(7), 1346–1351.e2. https://doi.org/10.1016/j.cub.2020.03.022

Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

Graphical Abstract of Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

- The study confirmed likeliness of SARS-CoV-2 presence in pangolins using pangolin lung samples from Liu’s study. By performing de novo assembly on 1,882 clean reads in a lung sample that covered 76.02% of the SARS-CoV-2 genome, they found that 22 out of 36 contigs best matched to SARS-CoV-2.
- A pangolin draft genome was created using a reference-guided scaffolding approach based on 34 contigs. There was a 99.99% genome coverage when comparing the draft genome to 1,882 clean reads, demonstrating that the draft genome can be reliably used for further analysis. Pangolin-CoV genome was found to be 91.02% identical to SARS-CoV-2 and 90.55% identical to RaTG13 using Simplot analysis. 

Pangolin-CoV is 91.02% identical to SARS-CoV-2 at the whole-genome level

Phylogenetic relationships were developed using whole genome sequences, RNA-dependent RNA polymerase genes, ORF1a and ORF1b (non-structural protein genes), and S and M gene-encoded structural proteins. All phylogenies support the close relationship between Pangolin-CoV, RaTG13, and SARS-CoV-2, with RaTG13 and SARS-CoV-2 being grouped together and Pangolin-CoV as a common ancestor. 

Pangolin-CoV is the second closest relative of SARS-CoV-2 behind RaTG13

The S1 protein in Pangolin-CoV is found to be more closely related to SARS-CoV-2 than to RaTG13 using an amino acid phylogenetic tree. The receptor-binding domain of the S1 protein of Pangolin-CoV and SARS-CoV-2 is highly conserved in five amino acid residues with only a difference in one other amino acid, demonstrating that both coronaviruses have similar pathogenic potential with one another. In contrast, four out of 5 of the key amino acid residues stated above are different in RaTG13. 

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