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Targeting enteroviral 2A protease by a 16-mer synthetic peptide: Inhibition of 2A-induced apoptosis in a stable Tet-on HeLa cell line |
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| Authors: | Nader Maghsoudi Narges Kh. Tafreshi Fariba Khodagholi Mitra Esfandiarei Marjan Sabbaghian Mahnaz Sajadi Maryam Moosavi |
| Affiliation: | a Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran b H. Lee Moffitt Cancer Center, Tampa, FL, USA c Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, NY, USA d Child & Family Research Institute, Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada e Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran f Department of Biology, Tofigh Daru Co., Tehran, Iran g Department of Physiology and Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran h School of basic science, Tarbiat Modares University, Tehran, Iran |
| Abstract: | Enteroviridae such as coxsackievirus are important infectious agents causing viral heart diseases. Viral protease 2A (2Apro) initiates the virus life cycle, and is an excellent target for developing antiviral drugs. Here, to evaluate the validity of the 2Apro as a proper therapeutic target, and based on the existing information and molecular dynamics, a 16-mer peptide was designed to specifically target the active site of protease 2Apro in order to block the activity of CVB3 2Apro. We showed that the peptide could compete with endogenous substrate in a concentration-dependent manner. Further, we established a HeLa cell line that expressed 2Apro. Expression of 2Apro resulted in significant morphological alteration and eventual cell death. Western blot and viability assay showed that the 16-mer peptide (200 μg/ml) could significantly block 2Apro activity and its cytotoxic effect. Future modification of the 16-mer peptide can improve its affinity for 2Apro and therefore develop effective antiviral drug. |
| Keywords: | CVB3 2A protease Apoptosis Caspase-3 |
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