Viroporin

Viroporins are small and usually hydrophobic multifunctional viral proteins that modify cellular membranes, thereby facilitating virus release from infected cells.

Many viroporins also have additional effects on cellular metabolism and homeostasis mediated by protein-protein interactions with host cell proteins.

[3][4][5] Viroporins are usually small - under 100 or 120 amino acid residues - and contain at least one region capable of folding into an amphipathic transmembrane helix.

[5] The most well-studied and well-established function of viroporins is the permeabilization of the cell membrane to ions and small solutes.

An alternative mechanism is illustrated by the SARS-CoV E protein, which forms a pore that integrates membrane lipids whose polar head groups influence ion selectivity.

[4] The homologous E protein of SARS-CoV-2 has been structurally characterized by solid-state NMR and found to form a pentamer permeable to cations.

Rotaviruses and picornaviruses, however, rely on their viroporins to facilitate the formation of viroplasm, or specialized intracellular compartments remodeled from the membrane of the endoplasmic reticulum in which genome replication occurs.

[3][9] Although many chemical compounds have been reported to interfere with the ion channel functions of various viroporins, clinical usage is relatively rare.

[20] Viroporins can be found in a large number of viruses with distinct genomic organizations and replication mechanisms.

The transmembrane helical tetramer of the influenza A virus M2 protein , which functions as a proton channel , in complex with the channel-blocking drug amantadine (shown in red). Highly conserved tryptophan and histidine residues known to play key roles in mediating proton transport are shown as sticks. From PDB : 3C9J ​. [ 1 ]
Solid-state NMR -based model of the pentameric pore formed by the transmembrane helices of the SARS-CoV-2 E protein , which forms a viroporin permeable to cations . [ 13 ] [ 14 ] Rendered from PDB : 7K3G ​.