Anti‐viral Effects of Phosphatidylethanolamine‐targeting agents

Abstract

Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are segregated to the inner leaflet of the plasma membrane of resting mammalian cells. We have previously shown that PS is exposed on the outer surface of virus‐infected cells and on enveloped viruses that bud out of these virus‐infected cells. The internal positioning of PS is maintained by aminophospholipid translocase, suggesting that this transporter is inhibited during viral infection. Because aminophospholipid translocase tranports both PS and PE from the outer to the inner leaflets of the plasma membrane, we hypothesized that PE would also be exposed on the outer surface of virus‐infected cells and on enveloped viruses. If so, the external PE could serve as a target for anti‐viral therapy. To target PE, we modified the 19‐amino‐acid PE‐binding tetracyclic peptide duramycin by conjugating it to biotin (DLB). The modification reduces the hemolytic activity and toxicity of the peptide but retains its PE binding abilities. DLB neutralizes multiple viruses in vitro. DLB also shows therapeutic efficacy in a lethal murine model for human cytomegalovirus. Our study demonstrates the promise of using PE as a target for broad‐spectrum anti‐viral drugs.