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Characterization of the SARS-CoV-2 E Protein: Sequence, Structure, Viroporin, and Inhibitors - PubMed

Review

. 2021 Jun;30(6):1114-1130.

doi: 10.1002/pro.4075. Epub 2021 Apr 13.

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Review

Characterization of the SARS-CoV-2 E Protein: Sequence, Structure, Viroporin, and Inhibitors

Yipeng Cao et al. Protein Sci. 2021 Jun.

Erratum in

  • CORRIGENDUM.

    [No authors listed] [No authors listed] Protein Sci. 2021 Dec;30(12):2482. doi: 10.1002/pro.4216. Protein Sci. 2021. PMID: 34799955 Free PMC article. No abstract available.

Abstract

The COVID-19 epidemic is one of the most influential epidemics in history. Understanding the impact of coronaviruses (CoVs) on host cells is very important for disease treatment. The SARS-CoV-2 envelope (E) protein is a small structural protein involved in many aspects of the viral life cycle. The E protein promotes the packaging and reproduction of the virus, and deletion of this protein weakens or even abolishes the virulence. This review aims to establish new knowledge by combining recent advances in the study of the SARS-CoV-2 E protein and by comparing it with the SARS-CoV E protein. The E protein amino acid sequence, structure, self-assembly characteristics, viroporin mechanisms and inhibitors are summarized and analyzed herein. Although the mechanisms of the SARS-CoV-2 and SARS-CoV E proteins are similar in many respects, specific studies on the SARS-CoV-2 E protein, for both monomers and oligomers, are still lacking. A comprehensive understanding of this protein should prompt further studies on the design and characterization of effective targeted therapeutic measures.

Keywords: COVID-19; E protein; coronavirus; inhibitors; viroporin.

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Figures

FIGURE 1
FIGURE 1

The lipid envelope encloses the virus and facilitates the entry of the SARS‐coronavirus (CoV)‐2 E protein into the host cell. The E protein is translated in the endoplasmic reticulum (ER) and accumulates in the Golgi. Then, the E protein monomer self‐assembles into an oligomer that functions as an ion channel

FIGURE 2
FIGURE 2

Multiple sequence alignment of SARS‐coronavirus (CoV) and SARS‐CoV‐2. Sequences 1 and 2 represent whole E proteins, and 3 and 4 represent 3D structures with identified amino acid regions (black box: transmembrane domain (TMD), red box: substituted residue or deletion)

FIGURE 3
FIGURE 3

Molecular formula and 3D chemical structure of hexamethylene amiloride (HMA) and amantadine (AMT) (a and b). Docking region for HMA in the coronavirus (CoV)‐2 transmembrane domain (TMD) (c)

FIGURE 4
FIGURE 4

Molecular formulas and 3D chemical structures of memantine and gliclazide (a and b)

FIGURE 5
FIGURE 5

Molecular formulas and 3D chemical structures of ZINC23221929 (a) and ZINC06220062 (b). Cartoon representation of the binding mode of two ligands with the E protein (c)

FIGURE 6
FIGURE 6

Molecular formulas and 3D chemical structures of rutin and doxycycline (a and b). Docking region for rutin and doxycycline in the coronavirus (CoV)‐2 E protein (c)

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