Coronavirus envelope protein: current knowledge

Abstract

Background: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins.

Main body: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research.

Conclusions: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

Keywords: Assembly; Budding; Coronavirus; Envelope protein; Topology; Viroporin.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Amino Acid Sequence and Domains of the SARS-CoV E Protein. The SARS-CoV E protein consists of three domains, i.e. the amino (N)-terminal domain, the transmembrane domain (TMD), and the carboxy (C)-terminal domain. Amino acid properties are indicated: hydrophobic (red), hydrophilic (blue), polar, charged (asterisks) [78]

Fig. 2

Predicted interaction between SARS-CoV E and S proteins through disulphide bonds [79]

Fig. 3

Partial amino acid sequences of the E protein C-terminus for the different CoV genera. Red blocks represent the potential location of the predicted PBM motif [18]

Fig. 4

Model proposed by Hagemeijer, Monastyrska [177] for the induction of ER membrane curvature. The luminal loops of CoV nsp3 and 4 are required to initiate rearrangement of the ER membrane and produce the DMVs characteristically seen in CoV-infected cells

Fig. 5

Illustration of a typical viroporin structure and motifs. The pore of the viroporin (brown) is created by the amphipathic α-helix and the viroporin is anchored to a lipid bilayer by terminal positively charged residues (lysine or arginine). Conformational changes in the structure regulate the flow ions through the viroporin by opening (left) and closing (right) the pore [208]

Fig. 6

Mechanisms of interaction between small molecules and proteins, and protein-protein interactions. Left: The binding of biotin to avidin occurs in a deep groove, while the interaction between the human growth hormone (hGH) and the hGH receptor (hGHR) occurs over a larger, flatter area [254]