Refereed journal article or data article (A1)

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




List of AuthorsDaria 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

PublisherMDPI AG

Publication year2017

JournalViruses

Journal name in sourceViruses

Volume number9

Issue number10

Number of pages15

ISSN1999-4915

DOIhttp://dx.doi.org/10.3390/v9100271

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/27627275


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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Last updated on 2023-08-09 at 19:12