ArticleProtein science : a publication of the Protein Society2014
Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: insights into mechanisms of general viral fusion and inhibitor design.
Article in Protein science : a publication of the Protein Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Lipid acyl chain protrusion induced by the influenza virus hemagglutinin fusion peptide detected by NMR paramagnetic relaxation enhancement.Biophysical chemistry · 2023Article
- A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization.Biomolecules · 2023Review
- Interactions of SARS-CoV-2 and MERS-CoV fusion peptides measured using single-molecule force methods.Biophysical journal · 2023Article
- Investigation of SARS-CoV-2 RNA contamination in water supply resources of Tabriz metropolitan during a peak of COVID-19 pandemic.Sustainable water resources management · 2023Article
- Computational and comparative investigation of hydrophobic profile of spike protein of SARS-CoV-2 and SARS-CoV.Journal of biological physics · 2022Article
- Recent advances in developing small-molecule inhibitors against SARS-CoV-2.Acta pharmaceutica Sinica. B · 2022Review
- Synchronized attachment and the Darwinian evolution of coronaviruses CoV-1 and CoV-2.Physica A · 2021Article
- Factors influencing recovery of SARS-CoV-2 RNA in raw sewage and wastewater sludge using polyethylene glycol-based concentration method.Journal of biomolecular techniques : JBT · 2021Article
- Could the COVID-19 Positive Asymptomatic Tobacco Smoker be a Silent Superspeader?Acta bio-medica : Atenei Parmensis · 2021Article
- The novel SARS-CoV-2 pandemic: Possible environmental transmission, detection, persistence and fate during wastewater and water treatment.The Science of the total environment · 2021Review
- Dual function of sialic acid in gastrointestinal SARS-CoV-2 infection.Environmental toxicology and pharmacology · 2020Review
- Physicochemical properties of SARS-CoV-2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control.Electrophoresis · 2020Review
- Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity.Journal of virology · 2020Article
- A molecular epidemiological investigation of PEDV in China: Characterization of co-infection and genetic diversity of S1-based genes.Transboundary and emerging diseases · 2020Article
- Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike.Computational and structural biotechnology journal · 2020Article
- Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments.Frontiers in pharmacology · 2020Article
- A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.Science advances · 2019Article
- Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution.Acta crystallographica. Section D, Structural biology · 2018Article
- Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms.PloS one · 2018Article
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3 authors at 1 institution in 1 country.
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Abstract
Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation=0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.
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