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[Study on the inhibitory effect of antisense phosphorothioate oligodeoxynucleotide on coxsackie virus B replication

X Qi1, X Li, M Liu

  • 1Department of Epidemiology, Tianjin Medical University, Tianjin 300070, China.

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi = Zhonghua Shiyan He Linchuang Bingduxue Zazhi = Chinese Journal of Experimental and Clinical Virology
|August 11, 2001
PubMed
Abstract

Insights

Antisense phosphorothioate oligodeoxynucleotide (AODN) effectively inhibited Coxsackie Virus B3 (CVB3) replication in vitro. This specific AODN demonstrated dose-dependent antiviral activity against CVB3, highlighting its potential as a therapeutic agent.

Area of Science:

  • Virology
  • Molecular Biology
  • Antiviral Therapy

Background:

  • Coxsackie Virus B3 (CVB3) is a significant human pathogen.
  • Effective antiviral strategies against CVB3 are crucial for public health.
  • Antisense oligodeoxynucleotides (AODN) show promise as targeted antiviral agents.

Purpose of the Study:

  • To evaluate the in vitro antiviral efficacy of a specific antisense phosphorothioate oligodeoxynucleotide (AODN).
  • To investigate the inhibitory effect of AODN on CVB3 replication in Vero cells.
  • To compare the antiviral activity of AODN with sense (SODN) and randomized (RODN) oligodeoxynucleotides.

Main Methods:

  • Synthesis of a 21-mer AODN targeting the 5' NCR of CVB3 RNA (nt 581-601).
  • Transfection of CVB3-infected Vero cells with varying concentrations of AODN, SODN, and RODN using lipofectamine.
  • Assessment of antiviral effects through inhibition of cytopathic effect (CPE), cell viability (MTT assay), viral antigen and RNA levels (ELISA, dot blotting), and viral titers (TCID50).

Main Results:

  • AODN significantly inhibited CVB3-induced CPE, viral antigen and RNA production, and viral titers in a dose-dependent manner.
  • Optimal inhibition was observed at 48 hours post-transfection with 10 µmol/L AODN, which also enhanced cell survival rates.
  • SODN exhibited a weaker inhibitory effect on CPE, while RODN showed no antiviral activity; AODN did not inhibit HSV-1 but showed some effect against other enteroviruses like Polio-1 and Echo-6.

Conclusions:

  • The 5' NCR region (nt 581-601) of CVB3 RNA is critical for viral replication.
  • AODN targeting this region demonstrates significant potential for inhibiting CVB3 replication.
  • AODN represents a promising strategy for developing targeted antiviral therapies against CVB3 and potentially other enteroviruses.

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