CD8 T cell epitope generation toward the continually mutating SARS-CoV-2 spike protein in genetically diverse human population: Implications for disease control and prevention.
Result: Although we identified major mutations on CD8 T cell epitopes including L5F, D614G and G1124V for the SARS-CoV-2 S protein, the detailed mechanisms driving these mutations are not known.
Result: Effect of D614G mutation on CD8 T cell epitope generation.
Result: In addition, these mutations are exclusively L to F at position 5, D to G at position 614 and G to V at position 1124.
Result: Similarly, we reanalyzed the 9-mer CD8 T cell epitope for the reference S protein with a single D614G mutation.
Result: These results illustrated differential effects of D614G mutation on the ca
Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects.
Method: 293T cells were transfected with pcDNA3.1 plasmids expressing the wild-type or D614G SARS-CoV-2 S glycoproteins, which contain carboxy-terminal His6 tags, using Lipofectamine 3000.
Method: Lentivirus particles containing the wild-type or D614G S gp prepared as described above were used to measure the binding of soluble ACE2 (sACE2) to the viral spike and to study the effect of sACE2 binding on the shedding of the S1 gp from the spike.
Method: To prepare lentivirus (HIV-1) particles containing wild-type or D614G S gp, ~7 x 106 293T cells in T75 flasks were transfected with 7.5 microg of psPAX2 and 7.5 microg of the S-expressing pcDNA3.1 plasmid using Lipofec
An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2.
Introduction: It was active against the D614G variant spike protein and against a panel of beta coronavirus spike proteins and protected human ACE2 transgenic mice against infection.
Result: A variant SARS-CoV-2 containing a D614G point mutation in the spike protein has been found to be circulating in the human population with increasing prevalence.
Result: ACE2 Microbody Blocks Entry of Virus with D614G Spike.
Result: Analysis of the infectivity of the D614G and wild-type pseudotyped viruses on the panel of cell lines showed that the mutation increased the infectivity of virus 2- to 4-fold on 293T, ACE2.293T, Vero, and VeroE6 cells, consistent with previous reports.
Result: Different
COVID-19 outbreak in Malaysia: Decoding D614G mutation of SARS-CoV-2 virus isolated from an asymptomatic case in Pahang.
Method: The D614G mutant of the Spike protein was generated by Modeler 9.21.
Result: Among the common variants, the most frequent mutations are 23403 A > G (D614G, S gene), 241 C > T ( Discussion: At the same time, several reports documented that 23,403 A > G (D614G) missense mutation in the Spike protein enhanced the infectivity rate of the virus.
Discussion: We observed in our protein modeling analysis that TMPRSS2 binding to Spike protein is enhanced by this mutation of aspartic acid to glycine (D614G) as it resulted in increased hydrogen bonding interactions.
COVID-19 outbreak in Malaysia: Decoding D614G mutation of SARS-CoV-2 virus isolated from an asymptomatic case in Pahang.
Introduction: Here we extend our understanding of the spike D614G mutation by demonstrating that it shifts spike protein trafficking towards the lysosome and away from organelles of the biosynthetic secretory pathway.
Introduction: Shortly after its entry into the human population, a variant strain of SARS-CoV-2 arose that displays multiple hallmarks of increased viral fitness, including a higher rate of transmission, elevated viral load in vivo, and enhanced infectivity in vitro This variant contains a mutation in the spike gene, D614G, that replaces the aspartate at position 614 with a glycine.
Introduction: The spike S1 domain binds SARS-CoV-2 receptors, primarily angiotensin converting enzyme-2 (ACE2) but also neuropilin-1, and yet,
CoV2-ID, a MIQE-compliant sub-20-min 5-plex RT-PCR assay targeting SARS-CoV-2 for the diagnosis of COVID-19.
Abstract: Finally, we have designed an assay for the detection of the D614G mutation and show that all of the samples isolated in the Chelmsford, Essex area between mid-April and June 2020, have the mutant genotype whereas a sample originating in Australia was infected with the wild type genotype.
Method: In addition, the human SARS-CoV-2 (NC_045512.2) genomic sequence was imported to the Beacon Designer 8.2 qPCR assay design software package and an LNA-based genotyping assay for discriminating the D614G
Result: An analysis of all clinical samples using the D614G genotyping assay revealed that all isolates harboured the A to G transition, characteristic of the more infectious phenotype, whereas the control clinical sample and Twist BioScience control 1 were both wild type, A, at this location (supplementary data file, Table 7).
Table: D614G
Defusing SARS-CoV-2: Emergency Brakes in a Vaccine Failure Scenario.
Abstract: The timing and locus for the therapeutic intervention are dictated by the cell entry mechanism and by the selective advantage of the dominant D614G mutation.
SARS-CoV-2 Spike Alterations Enhance Pseudoparticle Titers and Replication-Competent VSV-SARS-CoV-2 Virus.
Abstract: Additionally, we engineered a replication-competent VSV (rVSV) virus to produce the S-D614G variant with a truncated cytoplasmic tail.
Abstract: While the particles can be used to assess S entry requirements, the rVSV G/SMet1D614G 21 virus has a poor specific infectivity (particle to infectious titer ratio).
Potentially adaptive SARS-CoV-2 mutations discovered with novel spatiotemporal and explainable AI models.
Abstract: Functional predictions from structural analyses indicate that, contrary to previous reports, the Asp614Gly mutation in the spike glycoprotein (S) likely reduced transmission and the subsequent Pro323Leu mutation in the RNA-dependent RNA polymerase led to the precipitous spread of the virus.
Introduction: Based on our models, we find that a widely distributed mutation in the spike glycoprotein, Asp614Gly, likely alters its quaternary structure conformation and dynamics, and it only became pervasive after a subsequent mutation in the RNA-dependent RNA polymerase
Figure: The mutation Asp614Gly is quite frequent (62% of sequences analyzed have it) (PDB id 6xr8).
COVID-19 outbreak in Malaysia: Decoding D614G mutation of SARS-CoV-2 virus isolated from an asymptomatic case in Pahang.
Discussion: A molecular virological study investigated the details of conformational changes between D614 and G614 variants, and showed that the D614G mutation shifts the S glycoprotein conformation to be more open, which could contribute to the increased efficiency of ACE2 binding and fusion.
Discussion: Evidence showed that the S glycoprotein D614G mutation could enhance the infectivity of SARS-CoV-2 by incorporating more spike proteins to the viral envelope, which thereby increases the chance of viral attaching in populations with lower expression of ACE2 in host cells.
Discussion: Further studies using reverse genetics are required to confirm the relevance of our findings, connecting the D614G mutation with different ACE2 expression levels.
SARS_CoV_2 mutation literature information.
PMID: 
2020
PloS one
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