Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
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 prema...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-09-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/9/10/271 |
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doaj-a2efcfb6a1b5438e8d4582f4bed8125b |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins Viruses apoptosis antiviral agent innate immunity host response |
| author_facet |
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 |
| author_sort |
Daria Bulanova |
| title |
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins |
| title_short |
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins |
| title_full |
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins |
| title_fullStr |
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins |
| title_full_unstemmed |
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins |
| title_sort |
antiviral properties of chemical inhibitors of cellular anti-apoptotic bcl-2 proteins |
| publisher |
MDPI AG |
| series |
Viruses |
| issn |
1999-4915 |
| publishDate |
2017-09-01 |
| description |
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. |
| topic |
apoptosis antiviral agent innate immunity host response |
| url |
https://www.mdpi.com/1999-4915/9/10/271 |
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doaj-a2efcfb6a1b5438e8d4582f4bed8125b2020-11-24T21:09:57ZengMDPI AGViruses1999-49152017-09-0191027110.3390/v9100271v9100271Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 ProteinsDaria Bulanova0Aleksandr Ianevski1Andrii Bugai2Yevhen Akimov3Suvi Kuivanen4Henrik Paavilainen5Laura Kakkola6Jatin Nandania7Laura Turunen8Tiina Ohman9Hanna Ala-Hongisto10Hanna M. Pesonen11Marika S. Kuisma12Anni Honkimaa13Emma L. Walton14Valentyn Oksenych15Martina B. Lorey16Dmitry Guschin17Jungmin Shim18Jinhee Kim19Thoa T. Than20So Young Chang21Veijo Hukkanen22Evgeny Kulesskiy23Varpu S. Marjomaki24Ilkka Julkunen25Tuula A. Nyman26Sampsa Matikainen27Jani S. Saarela28Famara Sane29Didier Hober30Gülsah Gabriel31Jef K. De Brabander32Miika Martikainen33Marc P. Windisch34Ji-Young Min35Roberto Bruzzone36Tero Aittokallio37Markus Vähä-Koskela38Olli Vapalahti39Arto Pulk40Vidya Velagapudi41Denis E. Kainov42Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandDepartment of Biochemistry and Developmental Biology, University of Helsinki, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandDepartment of Virology, University of Helsinki, Helsinki 00290, FinlandDepartment of Virology, University of Turku, Turku 20520, FinlandDepartment of Virology, University of Turku, Turku 20520, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandInstitute of Biotechnology, University of Helsinki, Helsinki 00014, FinlandBiomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, FinlandBiomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, FinlandBiomedicum Functional Genomics Unit (FuGU), Helsinki, Helsinki 00290, FinlandDepartment of Virology, University of Tampere, Tampere 33520, FinlandDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, NorwayUniversity of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, FinlandInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaDepartment of Virology, University of Turku, Turku 20520, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandDepartment of Biological and Environmental Science/Nanoscience center, University of Jyväskylä, Jyväskylä 40500, FinlandDepartment of Virology, University of Turku, Turku 20520, FinlandInstitute of Biotechnology, University of Helsinki, Helsinki 00014, FinlandUniversity of Helsinki and Helsinki University Hospital, Rheumatology, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandUniversity of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, FranceUniversity of Lille, CHU Lille laboratoire de Virologie, EA3610, F-59037 Lille, FranceHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, GermanyDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USADepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, SwedenInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitut Pasteur Korea, Gyeonggi-do 13488, KoreaInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandDepartment of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, FinlandInstitute of Technology, University of Tartu, Tartu 50090, EstoniaInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, FinlandViral 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.https://www.mdpi.com/1999-4915/9/10/271apoptosisantiviral agentinnate immunityhost response |