Abstract
SARS-CoV-2 envelope protein (S2-E) is a conserved membrane protein that is essential to coronavirus assembly and budding. Here, we describe the recombinant expression and purification of S2-E into amphipol-class amphipathic polymer solutions. The physical properties of amphipols underpin their ability to solubilize and stabilize membrane proteins without disrupting membranes. Amphipol delivery of S2-E to pre-formed planar bilayers results in spontaneous membrane integration and formation of viroporin ion channels. Amphipol delivery of the S2-E protein to human cells results in membrane integration followed by retrograde trafficking to a location adjacent to the endoplasmic reticulum-to-Golgi intermediate compartment (ERGIC) and the Golgi, which are the sites of coronavirus replication. Delivery of S2-E to cells enables both chemical biological approaches for future studies of SARS-CoV-2 pathogenesis and development of “Trojan Horse” anti-viral therapies. This work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- (SARS-CoV-2)
- Severe acute respiratory syndrome 2 virus
- (S2-E)
- SARS-CoV-2 envelope protein
- (ERGIC)
- endoplasmic reticulum-to-Golgi intermediate compartment
- (CoV)
- coronavirus
- (VLP)
- virus-like particle
- (ARDS)
- acute respiratory distress syndrome
- (NBD)
- nitrobenzoxadiazole
- (UPR)
- unfolded protein response
