Abietic acid targets RAN to restrict coxsackievirus B3 infection

Junbo Huang1, Qing Song1, Yanjun Di1

  • 1School of Medicine, Huaqiao University, Quanzhou, China.

Insights

Abietic acid (AA) effectively inhibits Coxsackievirus B3 (CVB3) replication by targeting the host protein RAN. This antiviral strategy shows promise for treating viral myocarditis (VMC) and related heart conditions.

Area of Science:

  • Virology
  • Immunology
  • Pharmacology

Background:

  • Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis (VMC), often leading to severe heart damage and heart failure.
  • Current clinical treatments for CVB3-induced VMC are limited, necessitating the development of novel therapeutic agents.

Purpose of the Study:

  • To investigate the antiviral activity of abietic acid (AA) against CVB3 infection.
  • To elucidate the mechanism of action of AA in inhibiting CVB3 replication.
  • To evaluate the therapeutic potential of AA in a preclinical model of viral myocarditis.

Main Methods:

  • In vitro antiviral assays were performed to determine the efficacy and safety of AA against CVB3 using HeLa cells.
  • Mechanistic studies identified Ras-related nuclear protein (RAN) as a host dependency factor for CVB3 replication.
  • In vivo studies utilized a murine model of CVB3-induced myocarditis to assess the therapeutic effects of AA.

Main Results:

  • Abietic acid demonstrated potent anti-CVB3 activity (EC50 = 12.16 μM) with good biosafety (SI = 26.90).
  • AA treatment significantly reduced RAN expression, restored nuclear translocation of p-STAT1/2, and enhanced interferon-stimulated gene responses.
  • In vivo, AA treatment improved survival rates, reduced viral load and inflammation in cardiac tissues, and mitigated myocardial injury.

Conclusions:

  • Ras-related nuclear protein (RAN) is identified as a novel antiviral target essential for CVB3 replication.
  • Abietic acid inhibits CVB3 infection through the RAN-p-STAT1/2 signaling pathway.
  • Abietic acid shows significant potential as a therapeutic agent for CVB3-associated viral myocarditis and other cardiovascular diseases.

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