A Syntenin Inhibitor Blocks Endosomal Entry of SARS-CoV-2 and a Panel of RNA Viruses

Viruses. 2022 Oct 6;14(10):2202. doi: 10.3390/v14102202.


Viruses are dependent on host factors in order to efficiently establish an infection and replicate. Targeting the interactions of such host factors provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking and has previously been shown to be important for human papilloma virus (HPV) infection. Here, we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection and strongly reduced flavivirus infection, which is completely dependent on receptor-mediated endocytosis for their entry. In conclusion, we have identified a novel broad spectrum antiviral inhibitor that efficiently targets a broad range of RNA viruses.

Keywords: CHIKV; SARS-CoV-2; flavivirus; peptide inhibitor; syntenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • COVID-19*
  • Humans
  • RNA Viruses*
  • SARS-CoV-2
  • Syntenins
  • Virus Internalization


  • Syntenins
  • Antiviral Agents

Grants and funding

This work was supported by the grants from the Swedish Foundation for Strategic research (Y.I., P.J.: SB16-0039), the Swedish Research Council (Y.I.: 2020-03380; P.J.: 2020-04395; A.K.Ö.: 2018-05851) and the Knut and Alice Wallenberg Foundation (Y.I., P.J. and A.K.Ö. via Science for Life Laboratory, KAW 2020.0241, V-2020-0699).