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Viruses. 2017 Sep 25;9(10). pii: E271. doi: 10.3390/v9100271.

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

Author information

1
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. daria.bulanova@helsinki.fi.
2
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. aleksandr.ianevski@helsinki.fi.
3
Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki 00290, Finland. andrii.bugai@helsinki.fi.
4
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. yevhen.akimov@helsinki.fi.
5
Department of Virology, University of Helsinki, Helsinki 00290, Finland. suvi.kuivanen@helsinki.fi.
6
Department of Virology, University of Turku, Turku 20520, Finland. hojpaa@utu.fi.
7
Department of Virology, University of Turku, Turku 20520, Finland. laura.kakkola@utu.fi.
8
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. jatin.nandania@helsinki.fi.
9
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. laura.turunen@helsinki.fi.
10
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland. tiina.ohman@helsinki.fi.
11
Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland. hanna.ala-hongisto@helsinki.fi.
12
Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland. hanna.m.pesonen@helsinki.fi.
13
Biomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, Finland. marika.kuisma@helsinki.fi.
14
Department of Virology, University of Tampere, Tampere 33520, Finland. Anni.Honkimaa@uta.fi.
15
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway. emma.l.walton@ntnu.no.
16
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway. valentyn.oksenych@ntnu.no.
17
University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland. martina.lorey@helsinki.fi.
18
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. albanec2@gmail.com.
19
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. jungmin.shim@ip-korea.org.
20
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. jinhee.kim@ip-korea.org.
21
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. thoa.than@ip-korea.org.
22
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. soyoung.chang@ip-korea.org.
23
Department of Virology, University of Turku, Turku 20520, Finland. veijo.hukkanen@utu.fi.
24
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. evgeny.kulesskiy@helsinki.fi.
25
Department of Biological and Environmental Science/Nanoscience center, University of Jyväskylä, Jyväskylä 40500, Finland. varpu.s.marjomaki@jyu.fi.
26
Department of Virology, University of Turku, Turku 20520, Finland. ilkka.julkunen@utu.fi.
27
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland. t.a.nyman@medisin.uio.no.
28
Department of Immunology, University of Oslo, Oslo 0424, Norway. t.a.nyman@medisin.uio.no.
29
University of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, Finland. sampsa.matikainen@helsinki.fi.
30
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. jani.saarela@helsinki.fi.
31
University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France. famara.sane@chru-lille.fr.
32
University of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, France. didier.hober@chru-lille.fr.
33
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, Germany. guelsah.gabriel@hpi.uni-hamburg.de.
34
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA. jef.debrabander@utsouthwestern.edu.
35
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden. miika.martikainen@igp.uu.se.
36
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. marc.windisch@ip-korea.org.
37
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. jiyoung.min@ip-korea.org.
38
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. bruzzone@hkucc.hku.hk.
39
HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China. bruzzone@hkucc.hku.hk.
40
Department of Cell Biology and Infection, Institut Pasteur, Paris 75015, France. bruzzone@hkucc.hku.hk.
41
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. tero.aittokallio@helsinki.fi.
42
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. markus.vaha-koskela@helsinki.fi.
43
Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland. olli.vapalahti@helsinki.fi.
44
Department of Veterinary Biosciences, University of Helsinki, Helsinki 00014, Finland. olli.vapalahti@helsinki.fi.
45
Institute of Technology, University of Tartu, Tartu 50090, Estonia. arto.pulk@ut.ee.
46
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. vidya.velagapudi@helsinki.fi.
47
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland. denikaino@gmail.com.
48
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway. denikaino@gmail.com.
49
Institut Pasteur Korea, Gyeonggi-do 13488, Korea. denikaino@gmail.com.
50
Institute of Technology, University of Tartu, Tartu 50090, Estonia. denikaino@gmail.com.

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.

KEYWORDS:

antiviral agent; apoptosis; host response; innate immunity

PMID:
28946654
PMCID:
PMC5691623
DOI:
10.3390/v9100271
[Indexed for MEDLINE]
Free PMC Article

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