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 › peer-review

30 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
State	Published - Oct 2017

Keywords

Antiviral agent
Apoptosis
Host response
Innate immunity

ASJC Scopus subject areas

Infectious Diseases
Virology

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10.3390/v9100271

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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., ... Kainov, D. E. (2017). Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. Viruses, 9(10), Article 271. https://doi.org/10.3390/v9100271

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

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title = "Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins",

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",

author = "Daria Bulanova and Aleksandr Ianevski and Andrii Bugai and Yevhen Akimov and Suvi Kuivanen and Henrik Paavilainen and Laura Kakkola and Jatin Nandania and Laura Turunen and Tiina Ohman and Hanna Ala-Hongisto and Pesonen, {Hanna M.} and Kuisma, {Marika S.} and Anni Honkimaa and Walton, {Emma L.} and Valentyn Oksenych and Lorey, {Martina B.} and Dmitry Guschin and Jungmin Shim and Jinhee Kim and Than, {Thoa T.} and Chang, {So Young} and Veijo Hukkanen and Evgeny Kulesskiy and Marjomaki, {Varpu S.} and Ilkka Julkunen and Nyman, {Tuula A.} and Sampsa Matikainen and Saarela, {Jani S.} and Famara Sane and Didier Hober and G{\"u}lsah Gabriel and {De Brabander}, {Jef K.} and Miika Martikainen and Windisch, {Marc P.} and Min, {Ji Young} and Roberto Bruzzone and Tero Aittokallio and Markus V{\"a}h{\"a}-Koskela and Olli Vapalahti and Arto Pulk and Vidya Velagapudi and Kainov, {Denis E.}",

note = "Publisher Copyright: {\textcopyright} 2017 by the authors.Licensee MDPI, Basel, Switzerland.",

year = "2017",

month = oct,

doi = "10.3390/v9100271",

language = "English (US)",

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T1 - Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins

AU - Bulanova, Daria

AU - Ianevski, Aleksandr

AU - Bugai, Andrii

AU - Akimov, Yevhen

AU - Kuivanen, Suvi

AU - Paavilainen, Henrik

AU - Kakkola, Laura

AU - Nandania, Jatin

AU - Turunen, Laura

AU - Ohman, Tiina

AU - Ala-Hongisto, Hanna

AU - Pesonen, Hanna M.

AU - Kuisma, Marika S.

AU - Honkimaa, Anni

AU - Walton, Emma L.

AU - Oksenych, Valentyn

AU - Lorey, Martina B.

AU - Guschin, Dmitry

AU - Shim, Jungmin

AU - Kim, Jinhee

AU - Than, Thoa T.

AU - Chang, So Young

AU - Hukkanen, Veijo

AU - Kulesskiy, Evgeny

AU - Marjomaki, Varpu S.

AU - Julkunen, Ilkka

AU - Nyman, Tuula A.

AU - Matikainen, Sampsa

AU - Saarela, Jani S.

AU - Sane, Famara

AU - Hober, Didier

AU - Gabriel, Gülsah

AU - De Brabander, Jef K.

AU - Martikainen, Miika

AU - Windisch, Marc P.

AU - Min, Ji Young

AU - Bruzzone, Roberto

AU - Aittokallio, Tero

AU - Vähä-Koskela, Markus

AU - Vapalahti, Olli

AU - Pulk, Arto

AU - Velagapudi, Vidya

AU - Kainov, Denis E.

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Antiviral agent

KW - Apoptosis

KW - Host response

KW - Innate immunity

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U2 - 10.3390/v9100271

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AN - SCOPUS:85030546123

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VL - 9

JO - Viruses

JF - Viruses

IS - 10

M1 - 271

ER -

Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins

Abstract

Keywords

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