Viruses, Vol. 9, Pages 271: Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

Viruses, Vol. 9, Pages 271: Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

Viruses doi: 10.3390/v9100271

Authors: Daria Bulanova Aleksandr Ianevski Andrii Bugai Yevhen Akimov Suvi Kuivanen Henrik Paavilainen Laura Kakkola Jatin Nandania Laura Turunen Tiina Ohman Hanna Ala-Hongisto Hanna Pesonen Marika Kuisma Anni Honkimaa Emma Walton Valentyn Oksenych Martina Lorey Dmitry Guschin Jungmin Shim Jinhee Kim Thoa Than So Chang Veijo Hukkanen Evgeny Kulesskiy Varpu Marjomaki Ilkka Julkunen Tuula Nyman Sampsa Matikainen Jani Saarela Famara Sane Didier Hober Gülsah Gabriel Jef De Brabander Miika Martikainen Marc Windisch Ji-Young Min Roberto Bruzzone Tero Aittokallio Markus Vähä-Koskela Olli Vapalahti Arto Pulk Vidya Velagapudi Denis Kainov

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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