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Universal and mutation-resistant anti-enteroviral activity: potency of small interfering RNA complementary to the conserved cis-acting replication element within the enterovirus coding region

Hui Sun Lee^1,2,

Jeonghyun Ahn^1,2,

Heuiran Lee^1,2,

¹ Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea
² Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea
³ Division of Enteric and Hepatitis Viruses, Department of Virology, National Institute of Health, Korea Center for Disease Control and Prevention, Seoul, Korea
⁴ Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
⁵ Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea

Correspondence
Heuiran Lee
heuiran{at}amc.seoul.kr

The promising potential of RNA interference-based antiviral therapies has been well established. However, the antiviral efficacy is largely limited by genomic diversity and genetic instability of various viruses, including human enterovirus B (HEB). In this work, the first evidence supporting the anti-HEB activity of the small interfering RNA (siRNA) targeting the highly conserved cis-acting replication element (CRE) within virus coding region 2C is presented. HeLa cells pre-treated with siRNA complementary to the conserved sequence of the loop region of CRE(2C) were effectively rescued from the cytopathic effects of HEBs. Downregulation of virus replication and attenuation of cytotoxicity were consistently observed in various reference strains and clinical isolates. Cells treated with this siRNA were resistant to the emergence of viable escape mutants and showed sustained antiviral ability. Collectively, the data suggest that the siRNA based on the disordered structure within the highly conserved cis-acting coding region has potential as a universal, persistent anti-HEB agent. The same strategy can be successfully applied to the development of siRNA with consistent antiviral effects in other virus groups possessing similar RNA elements.

These authors contributed equally to this work.

Present address: Department of Microbiology, University of Ulsan College of Medicine, Songpa PO Box 145, Seoul, Korea.

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