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REVIEW Open Access Coronavirus envelope protein: current knowledge Dewald Schoeman and Burtram C. Fielding* 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: Coronavirus, Envelope protein, Topology, Assembly, Budding, Viroporin Background Coronaviruses (CoVs) (order Nidovirales, family Corona- viridae, subfamily Coronavirinae) are enveloped viruses with a positive sense, single-stranded RNA genome. With genome sizes ranging from 26 to 32 kilobases (kb) in length, CoVs have the largest genomes for RNA viruses. Based on genetic and antigenic criteria, CoVs have been organised into three groups: α-CoVs, β-CoVs, and γ-CoVs (Table 1) [1, 2]. Coronaviruses primarily infect birds and mammals, causing a variety of lethal diseases that particularly impact the farming industry [3, 4]. They can also infect humans and cause disease to varying de- grees, from upper respiratory tract infections (URTIs) resembling the common cold, to lower respiratory tract infections (LRTIs) such as bronchitis, pneumonia, and even severe acute respiratory syndrome (SARS) [5–14]. In recent years, it has become increasingly evident that human CoVs (HCoVs) are implicated in both URTIs and LRTIs, validating the importance of coronaviral research as agents of severe respiratory illnesses [7, 9, 15–17]. Some CoVs were originally found as enzootic infections, limited only to their natural animal hosts, but have crossed the animal-human species barrier and progressed to establish zoonotic diseases in humans [19–23]. Accordingly, these cross-species barrier jumps allowed CoVs like the SARS- CoV and Middle Eastern respiratory syndrome (MERS)- CoV to manifest as virulent human viruses. The consequent outbreak of SARS in 2003 led to a near pandemic with 8096 cases and 774 deaths reported worldwide, resulting in a © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: