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Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
Univ Helsinki, FIMM, Inst Mol Med Finland, FIN-00290 Helsinki, Finland..
Univ Helsinki, FIMM, Inst Mol Med Finland, FIN-00290 Helsinki, Finland..
Univ Helsinki, Dept Biochem & Dev Biol, FIN-00290 Helsinki, Finland..
Univ Helsinki, FIMM, Inst Mol Med Finland, FIN-00290 Helsinki, Finland..
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2017 (English)In: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 9, no 10, article id 271Article in journal (Refereed) Published
Abstract [en]

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.

Place, publisher, year, edition, pages
2017. Vol. 9, no 10, article id 271
Keywords [en]
apoptosis, antiviral agent, innate immunity, host response
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-341625DOI: 10.3390/v9100271ISI: 000414617500008OAI: oai:DiVA.org:uu-341625DiVA, id: diva2:1182050
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-02-12Bibliographically approved

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