Inhibition of respiratory syncytial virus by RhoA-derived peptides: implications for the development of improved antiviral agents targeting heparin-binding viruses.
The respiratory syncytial virus (RSV) fusion glycoprotein (F) can interact with the small intracellular GTPase RhoA, and peptides derived from RhoA inhibit RSV replication. These observations initially suggested that RhoA-derived peptides might inhibit RSV replication by disrupting an in vivo interaction between RSV F and RhoA. However, recent data indicate that the antiviral activity of RhoA-derived peptides is not due to competitive inhibition of an hypothesized F-RhoA interaction, but is rather a function of the peptides' intrinsic biophysical properties. We summarize here what is known about the mechanism of RSV inhibition by these peptides and give our opinion regarding the potential implications of this work with regards to RSV biology, and to the development of antiviral agents targeting RSV and other enveloped viruses.
Budge
Philip J
PJ
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Graham
Barney S
BS
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015704:CD4 Antigens / Q000737:chemistry; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000998:Antiviral Agents; D015704:CD4 Antigens; D010455:Peptides; D006493:Heparin; D020742:rhoA GTP-Binding Protein