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Viruses 2017, 9(10), 271;

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki 00290, Finland
Department of Virology, University of Helsinki, Helsinki 00290, Finland
Department of Virology, University of Turku, Turku 20520, Finland
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland
Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland
Department of Virology, University of Tampere, Tampere 33520, Finland
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway
University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland
Institut Pasteur Korea, Gyeonggi-do 13488, Korea
Department of Biological and Environmental Science/Nanoscience center, University of Jyväskylä, Jyväskylä 40500, Finland
Department of Immunology, University of Oslo, Oslo 0424, Norway
University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, Germany
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden
HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China
Department of Cell Biology and Infection, Institut Pasteur, Paris 75015, France
Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland
Department of Veterinary Biosciences, University of Helsinki, Helsinki 00014, Finland
Institute of Technology, University of Tartu, Tartu 50090, Estonia
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 26 August 2017 / Revised: 20 September 2017 / Accepted: 23 September 2017 / Published: 25 September 2017
(This article belongs to the Section Antivirals & Vaccines)
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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. View Full-Text
Keywords: apoptosis; antiviral agent; innate immunity; host response apoptosis; antiviral agent; innate immunity; host response

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bulanova, D.; Ianevski, A.; Bugai, A.; Akimov, Y.; Kuivanen, S.; Paavilainen, H.; Kakkola, L.; Nandania, J.; Turunen, L.; Ohman, T.; Ala-Hongisto, H.; Pesonen, H.M.; Kuisma, M.S.; Honkimaa, A.; Walton, E.L.; Oksenych, V.; Lorey, M.B.; Guschin, D.; Shim, J.; Kim, J.; Than, T.T.; Chang, S.Y.; Hukkanen, V.; Kulesskiy, E.; Marjomaki, V.S.; Julkunen, I.; Nyman, T.A.; Matikainen, S.; Saarela, J.S.; Sane, F.; Hober, D.; Gabriel, G.; De Brabander, J.K.; Martikainen, M.; Windisch, M.P.; Min, J.-Y.; Bruzzone, R.; Aittokallio, T.; Vähä-Koskela, M.; Vapalahti, O.; Pulk, A.; Velagapudi, V.; Kainov, D.E. Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins. Viruses 2017, 9, 271.

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