Peptides containing membrane-transiting motifs inhibit virus entry

Several exceptional peptides have been identified that can cross plasma membranes and deliver various covalently linked moieties into cells. We report the surprising observation that each of four structurally distinct transiting peptides tested displayed antiviral activity and inhibited herpes simplex virus entry into cells. All four peptides inhibited infection at concentrations in the low micromolar range. Some of the peptides selectively and reversibly blocked entry without inactivating virions in a persistent manner. For other peptides, the effects on virus entry were not readily distinguishable from virus inactivation. High concentrations of nearly all peptides lead to irreversible inactivation of virions. By various criteria, the peptides differed in their ability to inactivate virions and in the temperature dependence of inactivation. Testing of peptides with modifications known to disrupt transport revealed that, in some instances, transport activity did not correlate with antiviral activity. These results identify inhibition of viral entry as another common property of membrane-transiting peptides in addition to their ability to cross membranes and transport materials into cells. These or related peptides may be useful as agents to prevent infection and to study the process of viral entry.