TMPRSS2-specific antisense oligonucleotides inhibit host cell entry of emerging viruses.

Autor: Nowak R; Department of Molecular Virology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland., Gazecka M; Department of Molecular Virology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland., Hoffmann M; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg August University, Göttingen, Germany., Kierzek R; Department of Structural Chemistry and Biology of Nucleic Acids, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland., Pöhlmann S; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg August University, Göttingen, Germany., Zmora P; Department of Molecular Virology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland. Electronic address: pzmora@ibch.poznan.pl.
Jazyk: angličtina
Zdroj: Virology [Virology] 2024 Dec; Vol. 600, pp. 110218. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.virol.2024.110218
Abstrakt: Emerging viruses, such as novel influenza A viruses (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose a constant threat to animal and human health. Identification of host cell factors necessary for viral replication but dispensable for cellular survival might reveal novel, attractive targets for therapeutic intervention. Proteolytic activation of IAV hemagglutinin (HA) and SARS-CoV-2 spike protein (S) by the type II transmembrane serine protease (TTSPs), e.g. TMPRSS2 is sought to be critical for viral spread and pathogenesis. Here, we investigated the secondary structure of TMPRSS2 mRNA coding sequence and designed TMPRSS2-specific antisense oligonucleotides (ASOs). Several of these ASOs markedly reduced the TMPRSS2 expression and decreased IAV infection and SARS-CoV-2 entry into cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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