Viruses have evolved membrane-restructuring mechanisms for sustaining entry into cells, genome replication
and release from host cells. Picornavirus 2B, a non-structural protein required for effective viral replication, functions as a
potent intracellular pore-forming toxin by altering the permeability of cellular endomembranes. Two consecutive hydrophobic
regions have been identified in 2B protein that could function as an “-helix-turn--helix” hairpin membraneanchor.
A peptide derived from the first transmembrane domain comprised a “one-helix” 2B version that possesses the intrinsic
pore-forming activity required to directly and effectively permeabilize the cell plasma membrane. Moreover, this
miniaturized form is capable of translocating through the plasma membrane of culture cells and to target mitochondria.
These evidences suggest that viroporins constitute a new source of membrane-active sequences, worth exploring as potential
leads for the development of bioactive peptides, and/or as targets for the development of antiviral compounds.