The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Khan, Abbas; Gui, Jianjun; Ahmad, Waqar; Haq, Inamul; Shahid, Marukh; Khan, Amir Muhammad; Shah, Abdullah; Khan, Arsala; Ali, Liaqat; Anwar, Zeeshan; Safdar, Muhammad; Abubaker, Jehad; Uddin, Nizam; Cao, Liqiang; Wei, Dong‐Qing; Mohammad, Anwar

doi:10.1039/d1ra04694b

Cited by 57 publications

(73 citation statements)

References 62 publications

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“…This plays a significant role in understanding essential cellular functions. Thus, docking of the wild-type RBD with the ACE2 receptor revealed a docking score of −122.6 +/− 0.7, similar to that of previous studies [ 26 , 31 , 56 ]. However, the docking score for the B.1.620 RBD–ACE2 complex was reported to be −124.9 +/− 3.8, which is a higher docking score than that of the wild-type complex.…”

Section: Resultssupporting

confidence: 86%

“…Hence, a thorough investigation of the RBD-specific mutations, i.e., S477N and E484K, is required to reveal more information on this variant. For instance, a detailed analysis of the other variants (B.1.1.7, B.1.351, P.1, B.1.617, and B.1.618) using computational modeling and simulation approaches discovered that these mutations increase the binding affinity toward the host receptor and escape the antibody response [ 26 , 31 , 56 ]. To explore the role of these mutations and the impact on the binding of RBD with ACE2, we also employed molecular docking, hydrogen bonding network, and molecular dynamics simulation analyses to explore the variations in affinity and binding in comparison with the wild type.…”

Section: Resultsmentioning

confidence: 99%

“…Using HADDOCK, the wild-type and B.1.620 complexes (S477N-E484K) were subjected to interaction modeling to explore binding differences [ 44 ]. The interface residues were specified as reported previously, and restrained docking was performed [ 31 ]. For the wild type, the docking structures were provided by Professor Dong-Qing Wei [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…In SARS-CoV-2, the spike protein connects with the host ACE2, which allows the virus to attach and invade the host cell [ 30 ]. Two subunits of SARS-CoV-2 (S1 and S2) enable its transmission [ 31 ]. On infection, these subunits trigger the host’s immune system and provide an optimal means of innate immunity [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

Muhseen

Kadhim

Yahiya

et al. 2021

Biology

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Recently, a new variant, B.1620, with mutations (S477N-E484K) in the spike protein’s receptor-binding domain (RBD) has been reported in Europe. In order to design therapeutic strategies suitable for B.1.620, further studies are required. A detailed investigation of the structural features and variations caused by these substitutions, that is, a molecular level investigation, is essential to uncover the role of these changes. To determine whether and how the binding affinity of ACE2–RBD is affected, we used protein–protein docking and all-atom simulation approaches. Our analysis revealed that B.1.620 binds more strongly than the wild type and alters the hydrogen bonding network. The docking score for the wild type was reported to be −122.6 +/− 0.7 kcal/mol, while for B.1.620, the docking score was −124.9 +/− 3.8 kcal/mol. A comparative binding investigation showed that the wild-type complex has 11 hydrogen bonds and one salt bridge, while the B.1.620 complex has 14 hydrogen bonds and one salt bridge, among which most of the interactions are preserved between the wild type and B.1.620. A dynamic analysis of the two complexes revealed stable dynamics, which corroborated the global stability trend, compactness, and flexibility of the three essential loops, providing a better conformational optimization opportunity and binding. Furthermore, binding free energy revealed that the wild type had a total binding energy of −51.14 kcal/mol, while for B.1.628, the total binding energy was −68.25 kcal/mol. The current findings based on protein complex modeling and bio-simulation methods revealed the atomic features of the B.1.620 variant harboring S477N and E484K mutations in the RBD and the basis for infectivity. In conclusion, the current study presents distinguishing features of B.1.620, which can be used to design structure-based drugs against the B.1.620 variant.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

Muhseen

Kadhim

Yahiya

et al. 2021

Biology

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“…The entropic calculation was not conducted since it is a computationally expensive and time-consuming process and is also highly susceptible to significant inaccuracies [29].…”

Section: Estimation Of Binding Free Energymentioning

confidence: 99%

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

et al. 2021

Self Cite

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Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.

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SARS‐CoV‐2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID‐19 pandemic

Erabi,

Faridzadeh,

Parvin

et al. 2024

Health Science Reports

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Background and AimIn late 2021, the world faced the rapid spread of the SARS‐CoV‐2 Omicron variant, which quickly became the variant of concern. In April 2022, two new lineages of Omicron (BA.4/BA.5) emerged from Africa, where they caused the fifth wave of infection.MethodWe searched PubMed, Google Scholar, and Scopus online databases up to December 2023 for founding relevant studies.ResultsBA.4 and BA.5 subgroups, with changes in the spike protein, have a greater ability to escape from the immune system, which was possible with the help of L452R and F486V mutations. Epidemiologically, these evolving subtypes show similarities to seasonal influenza but with higher mortality rates. The symptoms of these subgroups are different from the previous types in the form of upper respiratory symptoms. Antiviral treatments, the use of antibodies such as bebtelovimab, and the development of vaccines are promising.ConclusionConsequently, we must continue to be vigilant in our joint surveillance efforts against COVID‐19 in diagnosis and treatment.

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The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Abstract: This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.

Cited by 57 publications

References 62 publications

Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

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

SARS‐CoV‐2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID‐19 pandemic

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