SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors

Rangel, Héctor R.; Ortega, Joseph T.; Maksoud, Semer; Pujol, Flor H.; Serrano, María Luisa

doi:10.1016/j.virusres.2020.198154

Cited by 15 publications

(14 citation statements)

References 49 publications

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“…This is the first study to be reported, where 16 different mammalian species were categorized for susceptibility to infection based on the structural molecular interactions and the presence of active glycosylation sites in the ACE2 receptor. Our study correlates well with a previously reported study where cats and ferrets are reported as highly susceptible compared to dogs, pigs and mice (Rangel et al 2020 ) . However, the study reported by Shen et al (Shen et al 2020 ) described both cats and dogs are prone to infection than other species in their study.…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 93%

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

et al. 2021

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“…We and others [16][17][18] have postulated that structural variation in different species of ACE2 might determine S protein binding and thereby determine which species are permissive to SARS-CoV-2 infection 19 . For example, the low binding affinity of S protein for mouse ACE2 likely explains why mice are not susceptible to SARS-CoV2 infection.…”

mentioning

confidence: 99%

In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin

Piplani

Singh

Winkler

et al. 2021

Sci Rep

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The devastating impact of the COVID-19 pandemic caused by SARS–coronavirus 2 (SARS-CoV-2) has raised important questions about its origins and the mechanism of its transfer to humans. A further question was whether companion or commercial animals could act as SARS-CoV-2 vectors, with early data suggesting susceptibility is species specific. To better understand SARS-CoV-2 species susceptibility, we undertook an in silico structural homology modelling, protein–protein docking, and molecular dynamics simulation study of SARS-CoV-2 spike protein’s ability to bind angiotensin converting enzyme 2 (ACE2) from relevant species. Spike protein exhibited the highest binding to human (h)ACE2 of all the species tested, forming the highest number of hydrogen bonds with hACE2. Interestingly, pangolin ACE2 showed the next highest binding affinity despite having a relatively low sequence homology, whereas the affinity of monkey ACE2 was much lower despite its high sequence similarity to hACE2. These differences highlight the power of a structural versus a sequence-based approach to cross-species analyses. ACE2 species in the upper half of the predicted affinity range (monkey, hamster, dog, ferret, cat) have been shown to be permissive to SARS-CoV-2 infection, supporting a correlation between binding affinity and infection susceptibility. These findings show that the earliest known SARS-CoV-2 isolates were surprisingly well adapted to bind strongly to human ACE2, helping explain its efficient human to human respiratory transmission. This study highlights how in silico structural modelling methods can be used to rapidly generate information on novel viruses to help predict their behaviour and aid in countermeasure development.

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“…The obtained results indicated that the mutations that occurred in the RBD of the Omicron variant resulted in an increased number of interactions between the spike and ACE2 receptor, especially, the number of interactions associated with the charged residues was increased (Table 2). Importantly, it has been previously described that the interactions between the charged residues of the viral spike and the host ACE2 play a major role in the complex stabilization and host selectivity [7,18,19]. These changes in the number and type of interactions were reflected in a decreased binding free energy (Table 2) and a decrease in the electrostatic, van der Waals interactions, and desolvation energies with an overall lower haddock score obtained for the Omicron variant as compared to the WT variant (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

2021

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The rise of SARS-CoV-2 variants, with changes that could be related to an increased virus pathogenicity, have received the interest of the scientific and medical community. In this study, we evaluated the changes that occurred in the viral spike of the SARS-CoV-2 Omicron variant and whether these changes modulate the interactions with the angiotensin-converting enzyme 2 (ACE2) host receptor. The mutations associated with the Omicron variant were retrieved from the GISAID and covariants.org databases, and a structural model was built using the SWISS-Model server. The interaction between the spike and the human ACE2 was evaluated using two different docking software, Zdock and Haddock. We found that the binding free energy was lower for the Omicron variant as compared to the WT spike. In addition, the Omicron spike protein showed an increased number of electrostatic interactions with ACE2 than the WT spike, especially the interactions related to charged residues. This study contributes to a better understanding of the changes in the interaction between the Omicron spike and the human host ACE2 receptor.

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SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors

Abstract: Graphical abstract

Cited by 15 publications

References 49 publications

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

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

In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

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