A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses

PLoS Negl Trop Dis. 2013 Sep 12;7(9):e2430. doi: 10.1371/journal.pntd.0002430. eCollection 2013.


For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / metabolism*
  • Bunyaviridae / drug effects
  • Bunyaviridae / physiology*
  • Chlorocebus aethiops
  • Ebolavirus / drug effects
  • Ebolavirus / physiology
  • Mononegavirales / drug effects
  • Mononegavirales / physiology*
  • Vero Cells
  • Viral Fusion Proteins / metabolism*
  • Virus Internalization*


  • Antiviral Agents
  • Viral Fusion Proteins

Associated data

  • PDB/1RER
  • PDB/2EBO
  • PDB/3CSY
  • PDB/3J0C
  • PDB/4HJC

Grant support

Support for this research was provided by the Defense Threat Reduction Agency (DTRA, http://www.dtra.mil/) under project number 4.10062_09_RD_B and the United States Department of Defense (DoD) High-Performance Computing Modernization Program (http://www.hpcmo.hpc.mil/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.