The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous...

Area of Science:

• Virology
• Structural Biology
• Biophysics

Background:

• The SARS-CoV-2 envelope (E) protein is crucial for virion budding.
• Previous studies suggested E protein forms cation-selective ion channels.

Purpose of the Study:

• To investigate the ion selectivity of SARS-CoV-2 E protein channels.
• To determine if E protein forms specific calcium channels or excludes anions.

Main Methods:

• Electrophysiological experiments using SARS-CoV-2 E protein in planar lipid bilayers.
• Experiments mimicked the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane composition.
• Sedimentation velocity experiments to determine E protein oligomerization.

Main Results:

• SARS-CoV-2 E protein channels exhibit mild ion selectivity, dependent on the lipid environment.
• No evidence found for cation-specific channels or anion exclusion.
• E protein channels maintain a non-specific, multi-ionic character, even with calcium ions.
• Channel activation is independent of voltage, high calcium, or low pH.
• Sedimentation velocity suggests pentameric but dynamic and heterogeneous E protein oligomers.

Conclusions:

• The SARS-CoV-2 E protein does not form cation-selective channels.
• E protein channels are non-specific and their properties are influenced by the surrounding lipids.
• The dynamic and heterogeneous nature of E protein oligomers contributes to observed channel conductance variations.