SARS-CoV-2 vaccine-breakthrough infections (VBIs) by Omicron (B.1.1.529) variant and consequences in structural and functional impact
Cellular Signalling(2022)
Abstract
This study investigated the efficacy of existing vaccinations against hospitalization and infection due to the Omicron variant of COVID-19, particularly for those who received two doses of Moderna or Pfizer vaccines and one dose of a vaccine by Johnson & Johnson or who were vaccinated more than five months previously. A total of 36 variants in Omicron’s spike protein, targeted by all three vaccinations, have made antibodies less effective at neutralizing the virus. Genotyping of SARS-CoV-2 viral sequencing revealed clinically significant variants such as E484K in three genetic mutations (T95I, D614G, and del142-144). One woman displayed two of these mutations, indicating a potential risk of infection following successful immunization, as recently reported by Hacisuleyman (2021). We examined the effects of mutations on domains (NID, RBM, and SD2) found at the interfaces of spike domains Omicron B.1.1529, Delta/B.1.1529, Alpha/B.1.1.7, VUM B.1.526, B.1.575.2, and B.1.1214 (formerly VOI Iota). We tested the affinity of Omicron for hACE2 and found that the wild and mutant spike proteins were using atomistic molecular dynamics simulations. According to binding free energies calculated during mutagenesis, hACE2 bound Omicron spike more strongly than SARS-CoV-2 wild strain. T95I, D614G, and E484K are three substitutions that significantly contribute to the RBD, corresponding to hACE2 binding energies and a doubling of Omicron spike proteins’ electrostatic potential. Omicron appears to bind hACE2 with greater affinity, increasing its infectivity and transmissibility. The spike virus was designed to strengthen antibody immune evasion through binding while boosting receptor binding by enhancing IgG and IgM antibodies that stimulate human β -cell, as opposed to the wild strain, which has more vital stimulation of both antibodies.
* VBIs
: Vaccine-breakthrough infections
COVID-19
: Coronavirus
ACE2
: Angiotensin-Converting Enzyme 2
RBD
: Receptor-binding domain
NTD
: N-terminal domain
RBM
: Receptor binding motif
SD2
: Subdomain
AAS
: Amino acid substitutions
WHO
: World Health Organization
MD
: Molecular dynamics
WT
: Wild type
MT
: Mutant
dbSNP
: Single nucleotide polymorphism database
PDB
: Protein data bank
NVT
: Equilibrate the system
FASTA
: Fast Alignment Search Tool
SIFT
: Sorting intolerant from tolerant
SNAP
: Screening for non-acceptable polymorphisms
PROVEAN
: Protein variation effect analyzer
S1-CTD
: Predictor of human deleterious single nucleotide polymorphisms (PhD-SNP) Subunits C-terminal domain
RMSD
: Root-mean-square deviation
RMSF
: Root mean square fluctuation
TGF-b
: Transforming growth factor
IFN-g
: Interferon-gamma
SODA
: Protein solubility based on disorder and aggregation
PASTA
: Prediction of amyloid structural aggregation
VOC
: Variant of concern
SASA
: Solvent-accessible surface area
PLP
: Proteolipid protein
HR1 & 2
: Heptad repeat 1 heptad repeat 2
TA
: Transmembrane anchor
IT
: Intracellular tail
MOE
: Molecular operating environment
RSA
: Relative solvent accessibility
DC
: Dendritic cells
EP
: Electroporation
NID
: Immunomodulatory drugs
Rg
: Radius of gyration
VSV
: Vesicular stomatitis virus
EPI
: Enhancer Promoter Interactions
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