Unavailability of Intermediate Host between Bat and Human
SARS-COV2 virus uses key entry-point residues of RBD in S1 protein to bind with the ACE2 receptor of human through K31, E35, D38, M82 and K353 (7). Among them, K31 and K353 are the most important residues for effective SARS-COV2 binding. Analysis of these residues in ACE2 receptors in various animals [Fig. 1C] suggests that mouse and rat possess poor ACE2 receptors (H353 in both animals instead of K353; also mouse has N31 instead of K31) for SARS-COV2 attachment (7). By cloning and infectivity experiments, they also showed that Civet cats, T31 instead of K31 but with intact K353 in ACE2 receptor allows a moderate SARS-COV2 infection but not mouse or rat (absence of K353) and indicated that K353 of ACE2 may be the most crucial residue in terms of SARS-COV2 attachment. Other animals like Chimp, Rhesus monkey, monkey, cat, dog and pig have high identity with human ACE2 receptor protein sequence [Suppl Materials 3C ] and possess both K31 and K353 residues in their ACE2 receptor [Fig.1C ] that could serve as an excellent attachment point for SARS-COV2 RBM and could efficiently serve as an intermediate host before infecting human. Although these animals are artificially infectible with SARS-COV2 virus, none of these animals are found to be naturally harbored any SARS-COV2 or its nearby genetically related COV virus. Thus, the conjecture remains to be elucidated whether such an intermediate host between human and bat would be existed or be explored in future in nature.