Pathophysiology


Last updated: 2021 Sep 13
Total hit(s): 8
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The D614G mutation was introduced into Spike-pseudotyped lentivirus and complete SARS-CoV-2 virus via site-directed mutagenesis. The D614G mutant was shown to be up to 8-fold more effective at infecting cells than wild-type. The Spike variants did not differ significantly in terms of ACE2 receptor binding, but the G614 variant is more resistant to proteolytic cleavage in vitro and in human cells than the D614. This could have an impact on the efficacy of immunizations based on spikes. The G614 variant was found to be ~2.5 fold more resistant to cleavage in the host cell than the D614 variant in cells expressing Spike by transient transfection. Virions with the G614 variant were seen to have less Spike cleavage compared to the D614 variant. No significant difference between Spike D614 and Spike G614 incorporation into pseudotyped lentiviral particles was observed.
32587969
(bioRxiv)
PMID
32587969
Date of Publishing: 2020 Jun 15
Title The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Author(s) name Daniloski Z, Guo X, Sanjana NE.
Journal bioRxiv
Impact factor
Its not a journal
Citation count: 2
Date of Entry 2021 Sep 13


The in vitro studies on primate endothelial kidney cells (BGM) and human lung adenocarcinoma cells (Calu-3) indicated comparable replication kinetics with the wild-type but a significant difference was observed between cell lines for each strain. After infection with WT and ORF6 variants, Interferon-stimulated genes were upregulated, the latter inducing overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNF, for which high plasma levels is associated with severe COVID-19.
33399033
(Emerg Microbes Infect)
PMID
33399033
Date of Publishing: 2021 Jan 5
Title Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster 1 during routine genomic surveillance, Lyon, France
Author(s) nameQuéromès G, Destras G et al.
Journal Emerg Microbes Infect
Impact factor
5.84
Citation count: 1
Date of Entry 2021 Aug 6


Growth curves for GLA1 (N439/D614G) or GLA2 (N439K/D614G) virus isolates were assessed in Vero E6 cells with ACE2 and TMPRSS2 overexpression. No significant growth amongst the isolates were observed indicating that N439K mutation played no role in viral growth.
33621484
(Cell)
PMID
33621484
Date of Publishing: 2021 Jan 28
Title Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
Author(s) nameThomson EC, Rosen LE et al.
Journal Cell
Impact factor
27.35
Citation count: 1
Date of Entry 2021 Aug 6


The L452R mutation increases viral replication in VeroE6/TMPRSS2 cells.
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PMID
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Title An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity
Date of Entry 2021 Aug 6


Pseudovirus with L452R mutation showed higher infectivity in 293T cells (6.7- to 22.5-fold increase) and HAO cell line (5.8- to 14.7-fold increase) than D614G-Pseudovirus but slightly lower infectivity than N501Y-Pseudovirus. N501Y mutation was known to increase pseudovirus entry owing to its higher infectivity levels compared to D614G mutation.
33991487
(Cell)
PMID
33991487
Date of Publishing: 2021 Jun 24
Title Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant
Author(s) nameDeng X, Garcia-Knight MA et al.
Journal Cell
Impact factor
27.35
Citation count: 6
Date of Entry 18_28_28 Jul


A comparative cohort study was conducted on COVID 19 samples from two different variants Daxing B.1.1.7 and Shunyi B.1.470, to determine the clinical freatures of B.1.1.7 variant. 7 clinical features-fever, C-reactive protein, d-dimmer, serum Amyloid A, creative kinase, CD4+ T lymphocyte and ground glass opacity was more in the Daxing group (B.1.1.7) when compared to the Shunyi B.1.470 group Limitations of this study are - 1. Small sample size of the two groups and 2. Clinical feature of B.1.1.7 variant was not compared with SARS-COV2 variant other than B.1.470.
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PMID
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Date of Publishing: 2021 May 08
Title COVID-19 cases from the first local outbreak of SARS-CoV-2 B.1.1.7 variant in China presented more serious clinical features: a prospective, comparative cohort study
Date of Entry 18_28_28 Jul


N440K variant of SARS CoV2, one of the prevalent strains found in India during the second wave of pandemic, produced 10 times and 1000 fold higher infectious viral titers than A2a (prevalent) and A3i (less prevalent) strains respectively. The results were obtained when Caco2 and Calu-3 cell cultures were infected with 0.1 MOI of the three variants and supernatant was collected after 24, 48 and 72 hours post-infection. No correlation was found between the RNA content and infectivity of the strain.Owing to the fact that the variant with high reproducibility was least infectious, the importance of measuring infectious viral titres instead of RT-qPCR assays in comparative studies is highlighted. Sequencing of the samples will provide more insight in the mechanism of rapid spread of N440K variant.
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PMID
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Title N440K variant of SARS-CoV-2 has Higher Infectious Fitness
Date of Entry 18_28_28 Jul


A222V mutations in the spike region do not lead to very large increases in the spike-pseudotyped lentiviruses but show a 1.3-fold higher titer than the wild type. However, the 20E (EU1) variant does not gain any transmission advantage over the variant with the D614G mutation. Lentiviral particles pseudotyped with the D614G spike mutation showed very large titers, which seem to have increased the transmission fitness of the SARS-CoV-2 variant.
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PMID
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Title Emergence and spread of a SARS-CoV-2 variant through Europe in the summer of 2020
Date of Entry 18_28_28 Jul