Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Kazybay, Bexultan; Ahmad, Ashfaq; Mu, Chenglin; Mengdesh, Diana; Xie, Yingqiu

doi:10.1016/j.tmaid.2021.102242

Cited by 30 publications

(27 citation statements)

References 33 publications

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“…The Omicron variant is highly concerned globally because of its large number of mutations [40,41]. Several overlapping mutations have been observed in previous VOCs and VOIs.…”

Section: Discussionmentioning

confidence: 99%

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

et al. 2022

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The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00532-4.

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“…The Omicron variant is highly concerned globally because of its large number of mutations [40,41]. Several overlapping mutations have been observed in previous VOCs and VOIs.…”

Section: Discussionmentioning

confidence: 99%

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

et al. 2022

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“…Structure-prediction-based molecular docking analysis revealed that epidermal growth factor receptor might act as another potential acceptor in mutants having N501Y. Since several kinases are elevated in cancer patients, N501Y mutation containing lineages might have more detrimental consequences ( Kazybay et al, 2021 ).…”

Section: Mutations In Omicron and Their Biological Consequencesmentioning

confidence: 99%

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Khandia

Singhal

Alqahtani

et al. 2022

Environmental Research

248

196

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Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

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“…9 Overall, we further suggest six possible candidates and particularly silymarin that attained 15.0411Kcal/mol in docking and gained further fitness in terms of H-bonds in the pocket as compared to the other five candidates, suggesting the potent clinically targeting omicron through main protease 3CL Mpro besides targeting entry. 10…”

Section: Article In Pressmentioning

confidence: 99%

Targeting omicron and other reported SARS-CoV-2 lineages by potent inhibitors of main protease 3CL Mpro: Molecular simulation analysis

Saeed

Ahmad

Majaz

et al. 2022

Journal of Infection

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Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Cited by 30 publications

References 33 publications

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Targeting omicron and other reported SARS-CoV-2 lineages by potent inhibitors of main protease 3CL Mpro: Molecular simulation analysis

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