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

Abstract

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 Felis catus, Equus caballus, Panthera tigris altaica, as highly susceptible while Oryctolagus cuniculus, Bos Tauras, Ovis aries and Capra hircus as moderately susceptible species for infection. Similarly, the E. asinus, Bubalus bubalis, Canis lupus familiaris, Ailuropoda melaleuca and Camelus dromedarius are categorized as low susceptible with Loxodonta Africana, Mus musculus, Sus scrofa and Rattus rattus as least susceptible species for SARS-CoV-2 infection.

Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation

“…A previous study by Khan et al [ 31 ] showed that hACE2–RBD forms hydrogen bonds (H-bonds) with Glu30–Lys417, Glu35–Gln493, Glu38–Tyr449, Glu38–Gly496, Tyr41–Thr500, Tyr41–Thr500, Gln42–Gln498, Asn330–Thr500, Lys353–Gly502, Lys353–Gly496, and Lys353–Gln498, as well as a salt bridge between Glu30 and Lys417. Several other researchers also confirmed that the following residues were important in RBD attachment to hACE: Gly446, Tyr449, Leu455, Phe486, Gln493, Gly496, Gln498, Thr500, Asn501, and Gly502 [ 45 , 46 , 47 ]. Moreover, Phe486, Gln493, and Asn501 in RBD were the most important residues identified by the hACE2 receptor on infected human cells, which simplified the RBD–hACE2 interaction [ 31 , 48 ].…”

An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants

“…On the other hand, several studies have shown that the key amino acids from the RBD of SARS-CoV-2, Leu455, Phe486, Gln493, and Asn501 form stronger interactions with the host receptor, together with Lys417, thus causing SARS-CoV-2’s affinity for ACE2 to be 20 folds compared to SARS-CoV ( Lan et al, 2020 ; Yan et al, 2020 ). According to Koley et al (2021) , the interacting residues of RBD are Gln493, Tyr449, and Gly446. Khan et al (2021) , on the other hand, reported that hACE2-RBD forms hydrogen bonds between Glu30-Lys417, Glu35-Gln493, Glu38-Tyr449, Glu38-Gly496, Tyr41-Thr500, Tyr41-Thr500, Gln42-Gln498, Asn330-Thr500, Lys353-Gly502, Lys353-Gly496, and Lys353-Gln498, and also a salt bridge between amino acids Glu30 and Lys417.…”

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

“…According to the results of amino acid interactions, the bromelain-derived peptide was able to interact with the receptor-binding motif (RBM) of RBD by blocking unique residues designated as important in the binding of the human angiotensin-converting enzyme 2 (ACE2) cell receptor. The residues that are crucial for SARS-CoV-2 RBD binding to hACE2 are Gly446, Tyr449, Leu455, Phe486, Tyr491, Gln493, Gly496, Gln498, Thr500, Asn501, and Gly502 [ 66 , 67 , 68 , 69 ], as well as a salt bridge contributed by Lys417 [ 69 ]. The residues Phe486, Gln493, and Asn501 are the most important residues in the RBD identified by the hACE2 receptor on infected human cells because they facilitate RBD-hACE2 interaction [ 17 , 70 ].…”