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 journalArticle

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 languageEnglish (US)
Article number271
JournalViruses
Volume9
Issue number10
DOIs
Publication statusPublished - 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