@article{b746426797f24e99bd4661b2dc8d17d3,
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 = "Funding Information: Acknowledgments: We thank Michelle Becker and Dominic Roy at the Ottawa Hospital Research Institute for generating VA7-mCherry virus. We thank Maria Nurmi from the Institute for Molecular Medicine Finland (FIMM) High Throughput Biomedicine unit (HTB) for preparing pre-drugged assay plates and for assistance with the live cell microscopy. We thank Anirban Maitra from Anderson, USA, for the kind gift of pancreatic cancer cells Pa02C. This study was supported by the J&A Erkko foundation (to Denis E. Kainov.), the European Regional Development Fund, the Mobilitas Pluss Project MOBTT39 (to Denis E. Kainov), a University of Helsinki three-year research grant (No. 465/51/2014, to Denis E. Kainov), the Academy of Finland (grant No. SA259725 to Olli Vapalahti), the Sigrid Juselius Foundation (to Olli Vapalahti), the Robert A. Welch Foundation (grant No. I-1422, to Jef K. De Brabander), EA3610 University of Lille 2 and CHRU Lille grants (to Didier Hober), and the Bio&Medical Technology Development Program of the NRF, funded by the Ministry of Science, ICT and Future Planning, Republic of Korea (grant No. 1601-0302, to Ji-Young Min). Publisher Copyright: {\textcopyright} 2017 by the authors.Licensee MDPI, Basel, Switzerland.",
year = "2017",
month = oct,
doi = "10.3390/v9100271",
language = "English (US)",
volume = "9",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",
}