Highly conserved binding region of ACE2 as a receptor for SARS‐CoV‐2 between humans and Hippopotamus

ABSTRACT

Background Several cases of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS‐CoV‐2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. Mother and daughter of Hippopotamus amphibius (Hippo) at the Antwerp Zoo in Belgium have been reported infected with SARS‐CoV‐2. SARS‐CoV‐2 is believed to have been infected by the hippo caretaker. Objective These reports have influenced us to perform a comparative analysis among angiotensin‐converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide “353‐KGDFR‐357 (H.sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS‐CoV‐2 spike receptor binding domain (RBD). Methods/Results ACE2 works as a receptor for the SARS‐CoV‐2 spike glycoprotein between humans, dogs, cats, tigers, Hippo, and other animals, except for snakes. The three‐dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS‐CoV‐2 spike RBD of the Hippo ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (805 residues of the Hippo ACE2 available sequence vs 805 residues of the human ACE2) (Figure). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues 353‐KGDFR‐357 with humans, dogs, cats, tigers, Hippo, and other animals, except for snakes. Conclusion Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS‐CoV‐2 transmission from animals to humans.