Repurposing staples for viruses: applying peptide design to RSV prophylaxis
Sarah P. Katen, Terence S. Dermody
Sarah P. Katen, Terence S. Dermody
Published April 17, 2014
Citation Information: J Clin Invest. 2014;124(5):1889-1891. https://doi.org/10.1172/JCI75797.
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Commentary

Repurposing staples for viruses: applying peptide design to RSV prophylaxis

Abstract

Respiratory syncytial virus (RSV) is responsible for lower respiratory tract infections and annually results in 200,000 deaths worldwide. Despite the burden of RSV-associated disease, treatments and preventative measures are limited. In this issue of JCI, Bird and colleagues describe their work using a peptide stapling technique that allowed synthesis of a stable peptide mimic of a portion of the RSV fusion protein. Pretreatment of cells with the stable peptide effectively blocked virus entry. When introduced into mice prior to RSV exposure, the peptide produced a substantial prophylactic effect. This work provides a new way forward in RSV prevention.

Authors

Sarah P. Katen, Terence S. Dermody

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Figure 1

Inhibition of RSV fusion with stapled peptides.

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Inhibition of RSV fusion with stapled peptides. (A) RSV fusion. Prefusio...
(A) RSV fusion. Prefusion RSV-F, consisting of two 3-HBs (red and pink cylinders), inserts into the cell membrane (i). Structural rearrangement of RSV-F (ii) results in formation of a 6-HB that brings the two membranes together (iii) for fusion via a hemifusion intermediate (iv). (B) Inhibition by stapled peptides. The antiviral peptide SAH-RSVF (yellow cylinder) is an α-helical peptide (gray, inset) stapled with cross-links that span two helical turns (green, inset). The peptide mimics one of the fusion helices (i) and binds to RSV-F in the prefusion state (ii), blocking formation of the fusogenic 6-HB and preventing membrane fusion (iii).