Towards Dewetting Monoclonal Antibodies for Therapeutical Purposes

Dewetting transition - a concept borrowed from fluid mechanics -  is a physiological process which takes place inside the hydrophobic pores of ion channels.  This transient phenomenon causes a metastable state which forbids water molecules to cross the microscopic receptors’ cavities.  This leads to a decrease of conductance, a closure of the hole and, subsequently, severe impairment of cellular performance.  We suggest that  artificially-provoked dewetting transition in ion channels’ hydrophobic pores could stand for a molecular candidate to erase detrimental organisms, such as viruses, bacteria and cancer cells.  We describe a novel type of high-affinity monoclonal antibody, which: a) targets specific trans-membrane receptor structures of harmful or redundant cells; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flows inside ion channels.  Therefore, we achieve an artificial dewetting transition inside receptors’ cavities which causes transmembrane ionic flows discontinuity, channel blockage and subsequent damage of morbid cells.  As an example, we describe dewetting monoclonal antibodies targeting the M2 channel of the Influenza A virus: they might prevent water to enter the pores, thus leading to virion impairment.