Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis

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

doi:10.17179/excli2020-1167

Cited by 145 publications

(72 citation statements)

References 17 publications

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“…The viral spike participates in the interaction with the host receptor angiotensin-converting enzyme 2 (ACE2), which is highly expressed in human airway cells [6]. The wild-type (WT) SARS-CoV-2 spike already showed changes that likely increased the efficiency of the virus-ACE2 receptor interactions as compared to SARS-CoV [7]. Major changes were noted in the region located within the residues 493 and 505 [7].…”

Section: Introductionmentioning

confidence: 99%

“…The wild-type (WT) SARS-CoV-2 spike already showed changes that likely increased the efficiency of the virus-ACE2 receptor interactions as compared to SARS-CoV [7]. Major changes were noted in the region located within the residues 493 and 505 [7]. Thus, the SARS-CoV-2 viral variants could have a different transmissibility and response to neutralizing antibodies [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…In this sense, Ortega et al [ 71 ] suggest that mutations in the viral S protein sequence might be favoring human to human transmission. They observed changes that triggered significant effects on SARS-CoV-2 spike/ACE2 interaction and reduced the binding energy, compared to Bat-CoV spike/ACE2 interaction [ 71 ]. Therefore, specific changes, in the nature of residues or in the type of chemical interactions occurring between ligand and receptor, may be decisive.…”

Section: Resultsmentioning

confidence: 99%

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Oliveira

Cruz

Ricelli

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.

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“…The fully mutated structure of the spike protein was docked against the ACE2 protein to analyze the changes in their interactions. The obtained results indicate that despite the high number of mutations, the spike protein targets the same region of the ACE2 protein as the wild type spike protein (Ortega et al 2020 ). Although the N-terminus helixes of both wild-type and mutated spike proteins interact with the same region of the ACE2, the orientation of the interactions is different.…”

Section: Discussionmentioning

confidence: 97%

Pierce into Structural Changes of Interactions Between Mutated Spike Glycoproteins and ACE2 to Evaluate Its Potential Biological and Therapeutic Consequences

Hashemi

Zarei

Mubarak

et al. 2021

Int J Pept Res Ther

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The structural consequences of ongoing mutations on the SARS-CoV-2 spike-protein remains to be fully elucidated. These mutations could change the binding affinity between the virus and its target cell. Moreover, obtaining new mutations would also change the therapeutic efficacy of the designed drug candidates. To evaluate these consequences, 3D structure of a mutant spike protein was predicted and checked for stability, cavity sites, and residue depth. The docking analyses were performed between the 3D model of the mutated spike protein and the ACE2 protein and an engineered therapeutic ACE2 against COVID-19. The obtained results revealed that the N501Y substitution has altered the interaction orientation, augmented the number of interface bonds, and increased the affinity against the ACE2. On the other hand, the P681H mutation contributed to the increased cavity size and relatively higher residue depth. The binding affinity between the engineered therapeutic ACE2 and the mutant spike was significantly higher with a distinguished binding orientation. It could be concluded that the mutant spike protein increased the affinity, preserved the location, changed the orientation, and altered the interface amino acids of its interaction with both the ACE2 and its therapeutic engineered version. The obtained results corroborate the more aggressive nature of mutated SARS-CoV-2 due to their higher binding affinity. Moreover, designed ACe2-baased therapeutics would be still highly effective against covid-19, which could be the result of conserved nature of cellular ACE2. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10346-1.

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Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis

Cited by 145 publications

References 17 publications

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

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

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Pierce into Structural Changes of Interactions Between Mutated Spike Glycoproteins and ACE2 to Evaluate Its Potential Biological and Therapeutic Consequences

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