Inhibition of Enveloped RNA Virus Formation by Peptides Corresponding to Glycoprotein Sequences

Peptides, corresponding to amino acid sequences in the cytoplasmic domains of the transmembranal glycoproteins encoded by Sindbis and vesicular stomatitis viruses, inhibited release of virus particles and infectious virus when added to infected cells for a 2h period during a one-cycle growth curve. Each inhibitory peptide was specific for its intended virus. The shortest peptide with antiviral activity for Sindbis virus contained six amino acids, and a related peptide that was acylated at the amino terminus with octanoic acid was ten-fold more potent as an inhibitor. Neither of these peptides affected the synthesis of viral structural proteins, but a third peptide inhibited proteolytic processing of the Sindbis virus E2 glycoprotein. Inhibition of vesicular stomatitis virus particle release was dose-dependent in the range of 50–400 μg ml⁻¹ for a peptide corresponding to the G glycoprotein cytoplasmic domain. We postulate that these peptides competitively inhibit attachment of the glycoprotein to intracellular virus structures during assembly of the virion. Thus, drugs, based on peptides that mimic the protein-protein interactions required for virus assembly, may have therapeutic potential.