Structural analysis of COVID-19 spike protein in recognizing the ACE2 receptor of different mammalian species and its susceptibility to viral infection.

The pandemic COVID-19 was caused by a novel Coronavirus-2 (SARS-CoV-2) that infects humans through the binding of glycosylated SARS-CoV-2 spike 2 protein to the glycosylated ACE2 receptor. The spike 2 protein recognizes the N-terminal helices of the glycosylated metalloprotease domain in the human ACE2 receptor. To understand the susceptibility of animals for infection and transmission, we did sequence and structure-based molecular interaction analysis of 16 ACE2 receptors from different mammalian species with SARS-CoV-2 spike 2 receptor binding domain. Our comprehensive structure analysis revealed that the natural substitution of amino acid residues Gln24, His34, Phe40, Leu79 and Met82 in the N-terminal α1 and α2 helices of the ACE2 receptor results in loss of crucial network of hydrogen-bonded and hydrophobic interactions with receptor binding domain of SARS-CoV-2 spike protein. Another striking observation is the absence of N-glycosylation site Asn103 in all mammals and many species, lack more than one N-linked glycosylation site in the ACE2 receptor. Based on the loss of crucial interactions and the absence of N-linked glycosylation sites we categorized <i>Felis catus, Equus caballus, Panthera tigris altaica,</i> as highly susceptible while <i>Oryctolagus cuniculus, Bos Tauras, Ovis aries</i> and Capra hircus as moderately susceptible species for infection. Similarly, the <i>E. asinus</i>, <i>Bubalus bubalis, Canis lupus familiaris, Ailuropoda melaleuca</i> and <i>Camelus dromedarius</i> are categorized as low susceptible with <i>Loxodonta Africana, Mus musculus, Sus scrofa and Rattus rattus</i> as least susceptible species for SARS-CoV-2 infection. The online version contains supplementary material available at 10.1007/s13205-020-02599-2.