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A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Department of Chemistry—BMC, Uppsala University, Box 576, Husargatan 3, Uppsala, Sweden.
Center for Biopharmaceuticals, Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
Department of Chemistry—BMC, Uppsala University, Box 576, Husargatan 3, Uppsala, Sweden.
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2022 (English)In: Viruses, E-ISSN 1999-4915, Vol. 14, no 10, article id 2202Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 14, no 10, article id 2202
Keywords [en]
CHIKV, flavivirus, peptide inhibitor, SARS-CoV-2, syntenin
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-200890DOI: 10.3390/v14102202ISI: 000873879700001PubMedID: 36298757Scopus ID: 2-s2.0-85140802544OAI: oai:DiVA.org:umu-200890DiVA, id: diva2:1709622
Available from: 2022-11-09 Created: 2022-11-09 Last updated: 2024-01-17Bibliographically approved

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Lindquist, RichardÖverby, Anna K.

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