Highlights: SARS-CoV-2 E-Protein Structural Insight: A Potential Target for Vaccine Development and other Therapeutic Strategies

August 12, 2020

  • The outbreak of COVID-19 across the world has posed unparalleled and global challenges on multiple fronts.
  • Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication.
  • Using the bioinformatics and structural modelling approach, the study modeled the structure of the envelope (E)-protein of novel SARS-CoV-2.
  • The E-protein of this virus shares sequence similarity with that of SARS- CoV-1.
  • The E-protein is highly conserved in the N-terminus regions.
  • The coronavirus E-protein is a small membrane protein that has an important role in the assembly of virions.
  • Recent studies have indicated that the E-protein has functions during infection beyond assembly, including in virus departure and in the host stress response.
  • The E-protein has ion channel activity, interacts with host proteins, and may have multiple membrane topologies.
  • Compared to spike proteins, E-proteins are more consistent and less mutability among the isolated sequences.
  • Using homology modelling, the study found that the most favorable structure could function as a gated ion channel conducting H+ ions.
  • Combining pocket estimation and docking with water, the research determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E-protein in an ERGIC-mimic membrane.
  • The vesicular-tubular cluster or endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is an organelle in eukaryotic cells, and it mediates trafficking between the endoplasmic reticulum and Golgi complex, facilitating the sorting of cargo.
  • Additionally, two distinct “core” structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel.
  • The study propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis.
  • The study provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus.

Source:

Sarkar M, Saha S (2020) Structural insight into the role of novel SARS-CoV-2 E protein: A potential target for vaccine development and other therapeutic strategies. PLoS ONE 15(8): e0237300. https://doi.org/10.1371/journal.pone.0237300

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347032/

Appenzeller-Herzog C, Hauri HP (June 2006). “The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function”J. Cell Sci119 (Pt 11): 2173–83. doi:10.1242/jcs.03019PMID 16723730


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