scholarly journals ACE2 models of frequently contacted animals provide clues of their SARS‐CoV‐2 S protein affinity and viral susceptibility

2021 ◽  
Author(s):  
Cheng Ma ◽  
Caixia Gong
Keyword(s):  
S Protein ◽  
Viral Susceptibility ◽  
Protein Affinity

scholarly journals Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?

2021 ◽  
Vol 22 (3) ◽  
pp. 992
Author(s):  
Laura Kate Gadanec ◽  
Kristen Renee McSweeney ◽  
Tawar Qaradakhi ◽  
Benazir Ali ◽  
Anthony Zulli ◽  
...  
Keyword(s):  
Host Cells ◽  
Viral Immunity ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Viral Susceptibility ◽  
Neuropilin 1 ◽  
Multiple Receptors ◽  
Systemic Spread ◽  
Spread Of Infection

The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection. Studies have demonstrated interactions between S protein and innate immune system, including C-lectin type receptors (CLR), toll-like receptors (TLR) and neuropilin-1 (NRP1), and the non-immune receptor glucose regulated protein 78 (GRP78). Recognition of carbohydrate moieties clustered on the surface of the S protein may drive receptor-dependent internalization, accentuate severe immunopathological inflammation, and allow for systemic spread of infection, independent of ACE2. Furthermore, targeting TLRs, CLRs, and other receptors (Ezrin and dipeptidyl peptidase-4) that do not directly engage SARS-CoV-2 S protein, but may contribute to augmented anti-viral immunity and viral clearance, may represent therapeutic targets against COVID-19.

MiR-210 and miR-155 are Upregulated in CFBE Cells and Involved in Fe-S Protein Assembly via ISCU Downregulation as well as HO-1 Expression via BACH1.

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Chillappagari ◽  
V Garapati ◽  
P Mahavadi ◽  
O Stehling ◽  
R Lill ◽  
...  
Keyword(s):  
Protein Assembly ◽  
S Protein

scholarly journals Palmitoylation of SARS-CoV-2 S protein is essential for viral infectivity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhuanchang Wu ◽  
Zhaoying Zhang ◽  
Xin Wang ◽  
Jing Zhang ◽  
Caiyue Ren ◽  
...  
Keyword(s):  
Viral Infectivity ◽  
S Protein

scholarly journals The Functional Consequences of the Novel Ribosomal Pausing Site in SARS-CoV-2 Spike Glycoprotein RNA

2021 ◽  
Vol 22 (12) ◽  
pp. 6490
Author(s):  
Olga A. Postnikova ◽  
Sheetal Uppal ◽  
Weiliang Huang ◽  
Maureen A. Kane ◽  
Rafael Villasmil ◽  
...  
Keyword(s):  
Amino Acid ◽  
Insertion Sequence ◽  
Experimental Studies ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Furin Cleavage ◽  
New Host ◽  
S Protein ◽  
Furin Cleavage Site ◽  
Ribosome Pausing

The SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid -PRRA- insertion sequence at amino acid residues (aa) 681–684 that forms a new furin cleavage site in S protein as well as several new glycosylation sites. We studied various statistical properties of the -PRRA- insertion at the RNA level (CCUCGGCGGGCA). The nucleotide composition and codon usage of this sequence are different from the rest of the SARS-CoV-2 genome. One of such features is two tandem CGG codons, although the CGG codon is the rarest codon in the SARS-CoV-2 genome. This suggests that the insertion sequence could cause ribosome pausing as the result of these rare codons. Due to population variants, the Nextstrain divergence measure of the CCU codon is extremely large. We cannot exclude that this divergence might affect host immune responses/effectiveness of SARS-CoV-2 vaccines, possibilities awaiting further investigation. Our experimental studies show that the expression level of original RNA sequence “wildtype” spike protein is much lower than for codon-optimized spike protein in all studied cell lines. Interestingly, the original spike sequence produces a higher titer of pseudoviral particles and a higher level of infection. Further mutagenesis experiments suggest that this dual-effect insert, comprised of a combination of overlapping translation pausing and furin sites, has allowed SARS-CoV-2 to infect its new host (human) more readily. This underlines the importance of ribosome pausing to allow efficient regulation of protein expression and also of cotranslational subdomain folding.

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