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Antiviral potency of a siRNA targeting a conserved region of coxsackievirus A24
Authors:Jun Eun Jung  Nam Young Ran  Ahn Jeonghyun  Tchah Hungwon  Joo Chul Hyun  Jee Youngmee  Kim Yoo Kyum  Lee Heuiran
Institution:a Department of Microbiology, University of Ulsan College of Medicine, Songpa P.O. Box 145, Seoul, Republic of Korea
b Department of Ophthalmology, University of Ulsan College of Medicine, Seoul, Republic of Korea
c Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Republic of Korea
d Division of Enteric and Hepatitis Viruses, Department of Virology, National Institute of Health, Korea Center for Disease Control and Prevention, Ministry of Health and Welfare, Seoul, Republic of Korea
Abstract:Coxsackievirus A24 (CVA24) is responsible for acute hemorrhagic conjunctivitis, a highly contagious eye disease for which no prevention or treatment is currently available. We thus assessed the antiviral potential of a small interfering RNA (siRNA) targeting CVA24. HeLa cells with or without four different siRNAs complementary to 2C or 3D genome region, were challenged with various CVA24s. Among several siRNAs, a siRNA targeting the highly conserved genome region called the cis-acting replication element (CVA24-CRE), was the only siRNA that decreased virus replication and subsequent cytotoxicity by both CVA24 variant and clinical isolates. Furthermore, CVA24-CRE had effective antiviral activity against CVA24 in primary human conjunctival cells. In addition, CVA24-CRE was highly resistant to the emergence of genetically altered escape mutants. Collectively, the present study provides evidence that CVA24-CRE targeting a conserved viral genome region had universal, prolonged anti-CVA24 activity. This siRNA may thus hold a potential to act clinically as a novel anti-CVA24 agent.
Keywords:Coxsackievirus A24  Acute hemorrhagic conjunctivitis  Small-interfering RNA  Antiviral effect  cis-Acting replication element
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