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

doi:10.3390/v9100271

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 KimThoa 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

Research output: Contribution to journal › Article

8 Scopus citations

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.

Original language	English (US)
Article number	271
Journal	Viruses
Volume	9
Issue number	10
DOIs	https://doi.org/10.3390/v9100271
Publication status	Published - Oct 1 2017

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Keywords

Antiviral agent
Apoptosis
Host response
Innate immunity

ASJC Scopus subject areas

Infectious Diseases
Virology

Cite this

Bulanova, D., Ianevski, A., Bugai, A., Akimov, Y., Kuivanen, S., Paavilainen, H., ... Kainov, D. E. (2017). Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. Viruses, 9(10), [271]. https://doi.org/10.3390/v9100271

Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. / Bulanova, Daria; Ianevski, Aleksandr; Bugai, Andrii; Akimov, Yevhen; Kuivanen, Suvi; Paavilainen, Henrik; Kakkola, Laura; Nandania, Jatin; Turunen, Laura; Ohman, Tiina; Ala-Hongisto, Hanna; Pesonen, Hanna M.; Kuisma, Marika S.; Honkimaa, Anni; Walton, Emma L.; Oksenych, Valentyn; Lorey, Martina B.; Guschin, Dmitry; Shim, Jungmin; Kim, Jinhee; Than, Thoa T.; Chang, So Young; Hukkanen, Veijo; Kulesskiy, Evgeny; Marjomaki, Varpu S.; Julkunen, Ilkka; Nyman, Tuula A.; Matikainen, Sampsa; Saarela, Jani S.; Sane, Famara; Hober, Didier; Gabriel, Gülsah; De Brabander, Jef K.; Martikainen, Miika; Windisch, Marc P.; Min, Ji Young; Bruzzone, Roberto; Aittokallio, Tero; Vähä-Koskela, Markus; Vapalahti, Olli; Pulk, Arto; Velagapudi, Vidya; Kainov, Denis E.

In: Viruses, Vol. 9, No. 10, 271, 01.10.2017.

Research output: Contribution to journal › Article

Bulanova, D, Ianevski, A, Bugai, A, Akimov, Y, Kuivanen, S, Paavilainen, H, Kakkola, L, Nandania, J, Turunen, L, Ohman, T, Ala-Hongisto, H, Pesonen, HM, Kuisma, MS, Honkimaa, A, Walton, EL, Oksenych, V, Lorey, MB, Guschin, D, Shim, J, Kim, J, Than, TT, Chang, SY, Hukkanen, V, Kulesskiy, E, Marjomaki, VS, Julkunen, I, Nyman, TA, Matikainen, S, Saarela, JS, Sane, F, Hober, D, Gabriel, G, De Brabander, JK, Martikainen, M, Windisch, MP, Min, JY, Bruzzone, R, Aittokallio, T, Vähä-Koskela, M, Vapalahti, O, Pulk, A, Velagapudi, V & Kainov, DE 2017, 'Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins', Viruses, vol. 9, no. 10, 271. https://doi.org/10.3390/v9100271

Bulanova, Daria ; Ianevski, Aleksandr ; Bugai, Andrii ; Akimov, Yevhen ; Kuivanen, Suvi ; Paavilainen, Henrik ; Kakkola, Laura ; Nandania, Jatin ; Turunen, Laura ; Ohman, Tiina ; Ala-Hongisto, Hanna ; Pesonen, Hanna M. ; Kuisma, Marika S. ; Honkimaa, Anni ; Walton, Emma L. ; Oksenych, Valentyn ; Lorey, Martina B. ; Guschin, Dmitry ; Shim, Jungmin ; Kim, Jinhee ; Than, Thoa T. ; Chang, So Young ; Hukkanen, Veijo ; Kulesskiy, Evgeny ; Marjomaki, Varpu S. ; Julkunen, Ilkka ; Nyman, Tuula A. ; Matikainen, Sampsa ; Saarela, Jani S. ; Sane, Famara ; Hober, Didier ; Gabriel, Gülsah ; De Brabander, Jef K. ; Martikainen, Miika ; Windisch, Marc P. ; Min, Ji Young ; Bruzzone, Roberto ; Aittokallio, Tero ; Vähä-Koskela, Markus ; Vapalahti, Olli ; Pulk, Arto ; Velagapudi, Vidya ; Kainov, Denis E. / Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. In: Viruses. 2017 ; Vol. 9, No. 10.

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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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AU - Walton, Emma L.

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AU - Lorey, Martina B.

AU - Guschin, Dmitry

AU - Shim, Jungmin

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AU - Than, Thoa T.

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AU - Hukkanen, Veijo

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10.3390/v9100271