*4.1. Data Acquisition and Findings*

The ACE2 protein receptor sequences from nineteen species *Homo sapiens* (Human), *Capra hircus* (Domestic goat), *Pan troglodytes* (Chimpanzee), *Equus caballus* (Horse), *Salmo salar* (Atlantic salmon), *Mesocricetus auratus* (Golden hamster), *Rhinolophus ferrumequinum* (Greater horseshoe bat), *Pteropus alecto* (Black flying fox), *Mustela putorius furo* (Domestic ferret), *Danio rerio* (Zebrafish), *Manis javanica* (Sunda pangolin), *Sus scrofa* (Domestic pig), *Macaca mulatta* (Rhesus macaque), *Bos taurus* (Aurochs), *Pelodiscus sinensis* (Chinese soft-shelled turtle), *Pteropus vampyrus* (Large flying fox), *Rattus norvegicus* (Brown rat), *Felis catus* (Domestic cat), and *Gallus gallus* (Red jungle fowl) were derived from the NCBI database [35]. Nineteen species and their respective ACE2 protein accession IDs with length are presented in Table 2.


**Table 2.** Nineteen species and their associated ACE2 sequences.

The nearest neighborhood phylogeny of the nineteen species derived from the NCBI public server based on ACE2 protein sequence similarity is shown in Figure 16A [36].

**Figure 16.** ACE2 full-length sequence-based phylogeny among nineteen species (**A**) and its derived clusters (**B**).

ACE2 sequence similarity among the species derives six clusters as shown in (Figure 16B). The contact residues of the receptor-binding domain (RBD) of the spike protein (YP\_009724390.1) of SARS-CoV-2 with the homo sapiens ACE2 interface are presented in Table 3 [14].


**Table 3.** Contact residues of RBD spike protein of SARS-CoV-2 and Homo sapiens ACE2.

The three designated domains, D1 (aa 24–42), D2 (aa 79–84), and D3 (aa 330–393) respectively contain the residues which bind to the RBD of the S protein.
