title: Inhibition of Japanese encephalitis virus (JEV) replication by specific RNA aptamer against JEV methyltransferase.
abstract: Japanese encephalitis virus (JEV) is the most common etiological agent of epidemic viral encephalitis. JEV encodes a single methyltransferase (MTase) domain located at the N-terminal region of the viral nonstructural protein NS5. JEV MTase is essential for viral replication and specifically catalyzes methylation of the viral RNA cap, which occurs exclusively in the cytoplasm. Therefore, JEV MTase is a potential target for antiviral therapy. Here, we identified specific and avid RNA aptamer (Kd∼ 12 nM) with modified 2'-O-methyl pyrimidines against JEV MTase. The RNA aptamer efficiently inhibited viral cap methylation activity of MTase and interfered with JEV production in cells. Moreover, we generated a 24-mer truncated aptamer that could specifically bind to JEV MTase with high affinity (Kd∼16 nM). The 24-mer aptamer efficiently inhibited JEV production and replication in cells. Therefore, MTase-specific RNA aptamer might be useful as an anti-JEV agent.
authors.affiliation: Department of Integrated Life Sciences, Research Institute of Advanced Omics, Dankook University, Yongin, Republic of Korea.
authors.forename: Seung Ryul
authors.initials: SR
authors.lastname: Han
authors.affiliation: Department of Integrated Life Sciences, Research Institute of Advanced Omics, Dankook University, Yongin, Republic of Korea. Electronic address: SWL0208@dankook.ac.kr.
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D009690:Nucleic Acid Conformation; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D052156:SELEX Aptamer Technique; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; C096041:NS5 protein, flavivirus; D012315:RNA Caps; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D008780:Methyltransferases
keywords: Anti-viral agent; Japanese encephalitis virus; Methyltransferase; RNA aptamer