Viruses (Sep 2017)
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
- Daria Bulanova,
- Aleksandr Ianevski,
- Andrii Bugai,
- Yevhen Akimov,
- Suvi Kuivanen,
- Henrik Paavilainen,
- Laura Kakkola,
- Jatin Nandania,
- Laura Turunen,
- Tiina Ohman,
- Hanna Ala-Hongisto,
- Hanna M. Pesonen,
- Marika S. Kuisma,
- Anni Honkimaa,
- Emma L. Walton,
- Valentyn Oksenych,
- Martina B. Lorey,
- Dmitry Guschin,
- Jungmin Shim,
- Jinhee Kim,
- Thoa T. Than,
- So Young Chang,
- Veijo Hukkanen,
- Evgeny Kulesskiy,
- Varpu S. Marjomaki,
- Ilkka Julkunen,
- Tuula A. Nyman,
- Sampsa Matikainen,
- Jani S. Saarela,
- Famara Sane,
- Didier Hober,
- Gülsah Gabriel,
- Jef K. De Brabander,
- Miika Martikainen,
- Marc P. Windisch,
- Ji-Young Min,
- Roberto Bruzzone,
- Tero Aittokallio,
- Markus Vähä-Koskela,
- Olli Vapalahti,
- Arto Pulk,
- Vidya Velagapudi,
- Denis E. Kainov
Affiliations
- Daria Bulanova
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Aleksandr Ianevski
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Andrii Bugai
- Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki 00290, Finland
- Yevhen Akimov
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Suvi Kuivanen
- Department of Virology, University of Helsinki, Helsinki 00290, Finland
- Henrik Paavilainen
- Department of Virology, University of Turku, Turku 20520, Finland
- Laura Kakkola
- Department of Virology, University of Turku, Turku 20520, Finland
- Jatin Nandania
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Laura Turunen
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Tiina Ohman
- Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland
- Hanna Ala-Hongisto
- Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland
- Hanna M. Pesonen
- Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland
- Marika S. Kuisma
- Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland
- Anni Honkimaa
- Department of Virology, University of Tampere, Tampere 33520, Finland
- Emma L. Walton
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway
- Valentyn Oksenych
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway
- Martina B. Lorey
- University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland
- Dmitry Guschin
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Jungmin Shim
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Jinhee Kim
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Thoa T. Than
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- So Young Chang
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Veijo Hukkanen
- Department of Virology, University of Turku, Turku 20520, Finland
- Evgeny Kulesskiy
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Varpu S. Marjomaki
- Department of Biological and Environmental Science/Nanoscience center, University of Jyväskylä, Jyväskylä 40500, Finland
- Ilkka Julkunen
- Department of Virology, University of Turku, Turku 20520, Finland
- Tuula A. Nyman
- Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland
- Sampsa Matikainen
- University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland
- Jani S. Saarela
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Famara Sane
- University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France
- Didier Hober
- University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France
- Gülsah Gabriel
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, Germany
- Jef K. De Brabander
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA
- Miika Martikainen
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden
- Marc P. Windisch
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Ji-Young Min
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Roberto Bruzzone
- Institut Pasteur Korea, Gyeonggi-do 13488, Korea
- Tero Aittokallio
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Markus Vähä-Koskela
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Olli Vapalahti
- Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland
- Arto Pulk
- Institute of Technology, University of Tartu, Tartu 50090, Estonia
- Vidya Velagapudi
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- Denis E. Kainov
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
- DOI
- https://doi.org/10.3390/v9100271
- Journal volume & issue
-
Vol. 9,
no. 10
p. 271
Abstract
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.
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