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JAC Advance Access published online on July 14, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh355
© 2004 by The British Society for Antimicrobial Chemotherapy
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Leading article

Inhibition of respiratory syncytial virus by RhoA-derived peptides: implications for the development of improved antiviral agents targeting heparin-binding viruses

Philip J. Budge 1 * Barney S. Graham 2*

1 Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Viral Pathogenesis Laboratory, Vaccine Research Center-NIAID, National Institutes of Health, MSC 3017, Bldg. 40 Room 2502, 40 Convent Dr., Bethesda, MD, 20892-3017, USA
2 Viral Pathogenesis Laboratory, Vaccine Research Center-NIAID, National Institutes of Health, MSC 3017, Bldg. 40 Room 2502, 40 Convent Dr., Bethesda, MD, 20892-3017, USA

* To whom correspondence should be addressed. E-mail: bgraham{at}nih.gov.


  Abstract

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.

Keywords: RSV; polyanions; fusion inhibition; dextran sulphate; sulphated polysaccharides; antiviral agents; post-attachment neutralization; human immunodeficiency virus; HIV; heparin; heparan sulphate.

*Present address. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.


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