Studies have reported that the ACE2 gene is highly expressed on the skin and cornea of dogs. This could make dogs highly susceptible to SARS-CoV-2. Moreover, as you can see in the ACE2 phylogenetic tree below (Fig. 1), dogs are closer to humans than other mammals, indicating that they are more suitable as an animal model for COVID-19 study ^[1].

Fig. 1. Conservation analysis of ACE2 gene.

(Source: Sun et al., 2020 Atlas of ACE2 gene expression in mammals reveals novel insights in transmission of SARS-Cov-2, doi: https://doi.org/10.1101/2020.03.30.015644.)

Besides dogs, monkeys and apes are also susceptible to SARS-CoV-2. Several infection studies have shown that rhesus monkeys could be successfully infected with SARS-CoV-2, and subsequently develop COVID-19 like symptoms. The Cynomolgus ACE2 (Cat. # AC2-C52H7) developed by ACRO has been verified to have good binding activity with SARS-CoV-2 S1 protein and S RBD protein, which also confirms that cynomolgus ACE2 is highly homologous with Human ACE2 ^[3].

In summary, monkeys and dogs are better animal models for COVID-19 research.

Paguma larvata is an important host of SARS. Its ACE2 receptor protein also showed a very good binding ability to the S protein of SARS-CoV-2, though not comparable to human and cynomolgus ACE2. We did an ELISA assay to confirm this result. As you can see from the Fig. 2 below, the EC50s of paguma larvata ACE2 to SARS-CoV-2 S1 protein and S RBD protein were 52nM and 67nM, respectively. The EC50s of cynomolgus ACE2 to SARS-CoV-2 S1 protein and S RBD protein were 0.1 nM and 0.02 nM, respectively. The EC50s of human ACE2 to SARS-CoV-2 S1 protein and S RBD protein were 1.15 nM and 1.16 nM, respectively.

Fig.2 ELISA Binding activity results

We investigated the binding activity between the ACE2 of human, cynomolgus or paguma larvata, and the S RBD of SARS-CoV-2 using BLI. The results are summarized in Fig.3. The binding activities of human and cynomolgus ACE2 to the S RBD of SARS-CoV2 are much higher than paguma larvata ACE2.

Fig.3 BLI binding activity results

An SPR method was also used to investigate the binding affinity between paguma larvata ACE2 and S RBD or S1 protein of SARS and SARS-CoV-2. Based on the results in Fig.4, we concluded that paguma larvata ACE2 is more susceptible to SARS.

Fig.4 SPR binding activity results

ACROBiosystems has successfully developed ACE2 proteins for cynomolgus, rat, mouse, paguma larvata, human. The binding activity of these proteins has been verified by BLI and these proteins can be used for anti-SARS-CoV-2 research. (see Fig.2 ELISA Binding activity results above).

We also investigated the binding activity between the ACE2 of human, cynomolgus, paguma larvata and the S RBD of SARS-CoV-2 using BLI. The results are summarized in Fig.3. The binding activities of human and cynomolgus ACE2 are much higher than paguma larvata.

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Reference：

[1] Sun et al., 2020 Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2, doi: https://doi.org/10.1101/2020.03.30.015644

[2] Stawiski et al., 2020 Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility. doi: https://doi.org/10.1101/2020.04.07.024752

3] Melin et al., 2020 Comparative ACE2 variation and primate COVID-19 risk, https://doi.org/10.1101/2020.04.09.034967

4) Wrapp et al., 2020 Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. DOI: 10.1126/science. Abb 2507