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Caboxamycin Inhibits Heart Inflammation in a Coxsackievirus B3-Induced Myocarditis Mouse Model
Hong-Gi Kim1, Prima F Hillman2, You-Jeung Lee3
1Department of Biomedical Science, Jungwon University, Goesan-gun 28024, Chungbuk, Republic of Korea.
Insights
Caboxamycin, an antibiotic from marine bacteria, effectively combats Coxsackievirus B3 (CVB3) infection. This compound reduces viral RNA and protein, protects against cell death, and improves survival in a mouse model of CVB3 myocarditis.
Area of Science:
- Virology
- Microbiology
- Pharmacology
Background:
- Coxsackievirus B3 (CVB3) is a major cause of human myocarditis and pancreatitis.
- Current treatments and vaccines for CVB3 are lacking.
- Marine-derived compounds offer potential therapeutic avenues.
Purpose of the Study:
- To investigate the antiviral activity of caboxamycin against CVB3.
- To elucidate the mechanism of action of caboxamycin in CVB3 infection.
- To evaluate the therapeutic potential of caboxamycin in a CVB3 myocarditis model.
Main Methods:
- In vitro antiviral assays using CVB3-infected HeLa cells.
- Western blot analysis to assess viral protein production and host factor cleavage.
- Quantitative analysis of viral RNA.
- Assessment of apoptosis-related molecule cleavage.
- In vivo studies using a CVB3-induced myocarditis mouse model.
Main Results:
- Caboxamycin significantly reduced CVB3 VP1 production and eIF4G1 cleavage.
- Viral positive and negative strand RNA levels were dramatically decreased by caboxamycin.
- Cleavage of pro-apoptotic molecules (BAD, BAX, caspase3) was inhibited.
- Caboxamycin treatment improved survival rates in mice.
- Reduced myocardial damage and inflammatory cell infiltration were observed in treated mice.
Conclusions:
- Caboxamycin exhibits potent antiviral activity against CVB3.
- The drug mechanism involves inhibition of viral replication and host cell apoptosis.
- Caboxamycin demonstrates significant therapeutic potential for CVB3-induced myocarditis.
Abstract:
Coxsackievirus B3 (CVB3) is a positive single-strand RNA genome virus which belongs to the enterovirus genus in the picornavirus family, like poliovirus. It is one of the most prevalent pathogens that cause myocarditis and pancreatitis in humans. However, a suitable therapeutic medication and vaccination have yet to be discovered. Caboxamycin, a benzoxazole antibiotic isolated from the culture broth of the marine strain Streptomyces sp., SC0774, showed an antiviral effect in CVB3-infected HeLa cells and a CVB3-induced myocarditis mouse model. Caboxamycin substantially decreased CVB3 VP1 production and cleavage of translation factor eIF4G1 from CVB3 infection. Virus-positive and -negative strand RNA was dramatically reduced by caboxamycin treatment. In addition, the cleavage of the pro-apoptotic molecules BAD, BAX, and caspase3 was significantly inhibited by caboxamycin treatment. In animal experiments, the survival rate of mice was improved following caboxamycin treatment. Moreover, caboxamycin treatment significantly decreased myocardial damage and inflammatory cell infiltration. Our study showed that caboxamycin dramatically suppressed cardiac inflammation and mouse death. This result suggests that caboxamycin may be suitable as a potential antiviral drug for CVB3.
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