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Viruses 2017, 9(10), 271; doi:10.3390/v9100271

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

1
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland
2
Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki 00290, Finland
3
Department of Virology, University of Helsinki, Helsinki 00290, Finland
4
Department of Virology, University of Turku, Turku 20520, Finland
5
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland
6
Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland
7
Department of Virology, University of Tampere, Tampere 33520, Finland
8
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway
9
University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland
10
Institut Pasteur Korea, Gyeonggi-do 13488, Korea
11
Department of Biological and Environmental Science/Nanoscience center, University of Jyväskylä, Jyväskylä 40500, Finland
12
Department of Immunology, University of Oslo, Oslo 0424, Norway
13
University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France
14
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, Germany
15
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA
16
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden
17
HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China
18
Department of Cell Biology and Infection, Institut Pasteur, Paris 75015, France
19
Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland
20
Department of Veterinary Biosciences, University of Helsinki, Helsinki 00014, Finland
21
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)
View Full-Text   |   Download PDF [4754 KB, uploaded 25 September 2017]   |  

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. 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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