The SARS-CoV heptad repeat 2 exhibits pH-induced helix formation

Celigoy, Jessica; McReynolds, Susanna; Caffrey, Michael

doi:10.1016/j.bbrc.2011.07.126

Cited by 4 publications

(9 citation statements)

References 20 publications

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“…On the other hand, the ability of HR2 to assume different structures may have functional ramifications for the entry mechanism. 13,15,16,20 As noted above, intermediate paramagnetic relaxation enhancement was observed for HR2 residues that are sequentially distant from the spin label under aqueous conditions. Previously, we have shown by CD, NMR, and analytical ultracentrifugation that HR2 exhibits a monomer-trimer equilibrium and that the monomer is unstructured.…”

Section: Resultsmentioning

confidence: 53%

“…On the other hand, the ability of HR2 to assume different structures may have functional ramifications for the entry mechanism. 13 , 15 , 16 , 20 …”

Section: Resultsmentioning

confidence: 99%

“…Previously, we have shown by CD, NMR, and analytical ultracentrifugation that HR2 exhibits a monomer–trimer equilibrium and that the monomer is unstructured. 15 , 16 , 20 As a consequence, the intermediate effects shown in Figure 2(b) may be attributed to the approach of distant residues to the spin label attached to residue 14. To test the validity of this notion, we determined a family of HR2 structures without using experimentally determined NOE, H-bond, and dihedral restraints.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, we note that we have previously suggested that the flexibility of the unstructured state facilitates conformational changes that are necessary for envelope-mediated membrane fusion. 15 , 16 , 20 …”

Section: Resultsmentioning

confidence: 99%

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SARS‐CoV heptad repeat 2 is a trimer of parallel helices

Celigoy¹,

Ramirez²,

Caffrey³

2011

Protein Science

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In severe acute respiratory syndrome coronavirus, the envelope heptad repeat 2 (HR2) plays a critical role in viral entry. Moreover, HR2 is both the target for novel antiviral therapies and, as an isolated peptide, presents a potential antiviral therapeutic. The structure of HR2, as determined by NMR spectroscopy in the presence of the co-solvent trifluoroethanol (TFE), is a trimer of parallel helices, whereas the structure of HR2, as determined by X-ray crystallography, is a tetramer of anti-parallel helices. In this work, we added a nitroxide spin label to the N-terminal region of HR2 and used paramagnetic relaxation enhancement to assess the orientation of the HR2 helices under different solution conditions. We find that the relaxation effects are consistent with an orientation corresponding to a trimer of parallel helices in both the presence and absence of TFE. This work suggests that the different orientation and oligomerization states observed by NMR and X-ray are due to the 11 additional residues present at the N-terminus of the NMR construct.

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Section: Resultsmentioning

confidence: 53%

“…On the other hand, the ability of HR2 to assume different structures may have functional ramifications for the entry mechanism. 13 , 15 , 16 , 20 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

SARS‐CoV heptad repeat 2 is a trimer of parallel helices

Celigoy¹,

Ramirez²,

Caffrey³

2011

Protein Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…This results in the merging of viral and cellular membranes and ultimately fusing with the host cell membrane, allowing the viral genomic RNA to enter the cytosol. 44 The viral genome RNA consists of a replicase gene that encodes for two sizable ORFs (rep1a and rep1b), that undergoes translation producing two large overlapping polyproteins namely pp1a and pp1ab. 45 The expression of the two-terminal polyproteins was achieved by utilizing a slippery sequence (UUUAAAC) and an RNA pseudoknot which leads to a ribosomal frameshifting from rep1a reading frame to rep1b ORF.…”

Section: Life Cycle Of Sars Coronavirusesmentioning

confidence: 99%

Global Pandemic as a Result of Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak: A Biomedical Perspective

Vairavan¹,

Rameshnathan²,

Suryadevara³

et al. 2021

J. Pure Appl. Microbiol.

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In December 2019, a novel coronavirus had emerged in Wuhan city, China that led to an outbreak resulting in a global pandemic, taking thousands of lives. The infectious virus was later classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Individuals infected by this novel virus initially exhibit nonspecific symptoms such as dry cough, fever, dizziness and many more bodily complications. From the “public health emergency of international concern” declaration by the World Health Organisation (WHO), several countries have taken steps in controlling the transmission and many researchers share their knowledge on the SARS-COV-2 characteristics and viral life cycle, that may aid in pharmaceutical and biopharmaceutical companies to develop SARS-CoV-2 vaccine and antiviral drugs that interfere with the viral life cycle. In this literature review the origin, classification, aetiology, life cycle, clinical manifestations, laboratory diagnosis and treatment are all reviewed.

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Broad-Spectrum Coronavirus Inhibitors Discovered by Modeling Viral Fusion Dynamics

Reilly,

Moore,

Lightbown

et al. 2024

Preprint

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Broad-spectrum therapeutics capable of inhibiting SARS-CoV-2, its variants, and related coronaviruses hold promise in curbing the spread of COVID-19 and averting future pandemics. Here, we employed a multidisciplinary approach that included molecular dynamics simulation (MDS) and artificial intelligence (AI)-based docking predictions to identify potent inhibitors that target a conserved region within the SARS-CoV-2 spike protein that mediates membrane fusion by undergoing large-scale mechanical rearrangements. In silico binding screens honed in on this region, leading to the discovery of FDA-approved drugs and novel molecules predicted to disrupt spike protein conformational changes. These compounds significantly inhibited SARS-CoV-2 infection and blocked the entry of spike protein-bearing pseudotyped α, β, γ, δ variants as well as SARS-CoV and MERS-CoV in cultured human ACE2-expressing cells. The optimized lead compound significantly inhibited SARS-CoV2 infection in mice when administered orally.

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The SARS-CoV heptad repeat 2 exhibits pH-induced helix formation

Cited by 4 publications

References 20 publications

SARS‐CoV heptad repeat 2 is a trimer of parallel helices

SARS‐CoV heptad repeat 2 is a trimer of parallel helices

Global Pandemic as a Result of Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak: A Biomedical Perspective

Broad-Spectrum Coronavirus Inhibitors Discovered by Modeling Viral Fusion Dynamics

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