Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity

Khan, Abbas; Mohammad, Anwar; Haq, Inamul; Nasar, M.; Ahmad, Waqar; Yousafi, Qudsia; Suleman, Muhammad; Ahmad, Sajjad; Albutti, Aqel; Khan, Taimoor; Marafie, Sulaiman K.; Alshawaf, Eman; Ali, Syed Shujait; Abubaker, Jehad; Wei, Dong‐Qing

doi:10.3390/microorganisms9112331

Cited by 9 publications

(8 citation statements)

References 37 publications

(77 reference statements)

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“…Together, the results presented in this study indicate that mutations that emerged in the new SARS-CoV-2 Omicron variant enhance the binding affinity of this variant to the host ACE2 receptor, which likely is an important driver of its increased transmissibility. However, it is important to note that SARS-CoV-2 besides ACE2 could also use other cellular receptors as a secondary binding way to target the host cells [19,[41][42][43]. Thus, it cannot be excluded that the changes that emerged in the Omicron viral spike could have an impact on the virus interaction with these secondary cellular receptors, additionally increasing the virus's ability to reach its target.…”

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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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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“…Changes in virus empirical formulas lead to changes in Gibbs energy. As a rule, strains with greater infectivity are characterized by more negative Gibbs energy of binding ( Khan et al, 2021a , 2021b ). The results of this research are in agreement with those of Han et al, (2021) , who found that the difference in Gibbs energies of binding between Hu-1 and 501Y (ΔΔ B G ) is between 10.61 kJ/mol and 19.97 kJ/mol.…”

Section: Discussionmentioning

confidence: 99%

Strain wars 2: Binding constants, enthalpies, entropies, Gibbs energies and rates of binding of SARS-CoV-2 variants

Popovic

2022

Virology

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“…For the template the reported co-crystal PDB ID: 6M17 was considered. HADDOCK enabled restraint docking of the wild type and mutant was considering the previous parameter [13][14][15][16][17]. A special interface, Guru Interface, was exploited to exercise all the available options for best docking [10,[17][18][19][20].…”

Section: Structural Modeling and Interaction Predictionmentioning

confidence: 99%

Structural communication fingerprinting and dynamic investigation of RBD-hACE2 complex from BA.1 × AY.4 recombinant variant (Deltacron) of SARS-CoV-2 to decipher the structural basis for enhanced transmission

Wang

Muhammad

Aman

et al. 2022

Journal of Biomolecular Structure and Dynamics

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The BA.1 x AY.4 recombinant variant (Deltacron) continues to inflict chaos globally due to its rapid transmission and infectivity. To decipher the mechanism of pathogenesis by the BA.1 x AY.4 recombinant variant (Deltacron), a protein coupling, protein structural graphs (PSG), residue communication and all atoms simulation protocols were used. We observed that the bonding network is altered by this variant; engaging new residues that helps to robustly bind. The protein structural graphs revealed variations in the hub residues, number of nodes, inter and intra residues communities, and path communication perturbation caused by the acquired mutations in the Deltacron-RBD thus alter the binding approach and infectivity. Moreover, the dynamic behaviour reported a highly flexible structure with enhanced residues flexibility particularly by the loops required for interaction with ACE2. It was observed that these mutations have altered the secondary structure of the RBD mostly transited to the loops thus acquired higher flexible dynamics than the native structure during the simulation. The total binding free energy for each of these complexes i.e. WT-RBD and Deltacron-RBD were reported to be -61.38 kcal/mol and -70.47 kcal/mol. Protein's motion revealed a high trace value in the Deltacron variant that clearly depict more structural flexibility. The broad range of phase space covered by the Deltacron variant along PC1 and PC2 suggests that these mutations are important in contributing conformational heterogeneity or flexibility that consequently help the variant to bind more efficiently than the wild type. The current study provide a basis for structure-based drug designing against SARS-CoV-2.

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Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity

Cited by 9 publications

References 37 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

Strain wars 2: Binding constants, enthalpies, entropies, Gibbs energies and rates of binding of SARS-CoV-2 variants

Structural communication fingerprinting and dynamic investigation of RBD-hACE2 complex from BA.1 × AY.4 recombinant variant (Deltacron) of SARS-CoV-2 to decipher the structural basis for enhanced transmission

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