Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins
Suvi Kuivanen; Andrii Bugai; Ji-Young Min; Roberto Bruzzone; Hanna M. Pesonen; Martina B. Lorey; Denis E. Kainov; Markus Vähä-Koskela; Gülsah Gabriel; Tuula A. Nyman; Aleksandr Ianevski; Tiina Ohman; Thoa T. Than; Miika Martikainen; Jani S. Saarela; Hanna Ala-Hongisto; So Young Chang; Didier Hober; Marc P. Windisch; Olli Vapalahti; Valentyn Oksenych; Evgeny Kulesskiy; Henrik Paavilainen; Tero Aittokallio; Vidya Velagapudi; Veijo Hukkanen; Famara Sane; Jungmin Shim; Yevhen Akimov; Jef K. De Brabander; Sampsa Matikainen; Laura Turunen; Ilkka Julkunen; Emma L. Walton; Laura Kakkola; Jatin Nandania; Arto Pulk; Jinhee Kim; Dmitry Guschin; Marika S. Kuisma; Anni Honkimaa; Daria Bulanova; Varpu S. Marjomaki
https://urn.fi/URN:NBN:fi-fe2021042717558
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]