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6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy
Qiao You1, Jing Wu1,2, Ruining Lyu1
1Center for Public Health Research, Medical School of Nanjing University, Nanjing, China.
BMC Microbiology
|January 29, 2025
Summary
6-thioguanine (6-TG) effectively inhibits enterovirus 71 (EV71) replication in cells. This FDA-approved drug shows potent antiviral activity against EV71, suggesting its potential for treating hand, foot, and mouth disease (HFMD).
Area of Science:
- Virology
- Pharmacology
- Molecular Biology
Background:
- Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease (HFMD) in children, with no specific treatments available.
- Previous research identified 6-thioguanine (6-TG), an anticancer drug, as a potential antiviral agent.
Purpose of the Study:
- To investigate the anti-EV71 activity of 6-thioguanine (6-TG).
- To explore the mechanism of 6-TG's antiviral effect against EV71.
Main Methods:
- EV71-infected HT-29 cells were treated with 6-TG.
- Viral mRNA levels, VP1 protein expression, and viral progeny were quantified.
- Cell viability, cytotoxicity (CC50), and inhibitory concentrations (IC50) were determined.
- The role of BIRC3 and autophagy in 6-TG's mechanism was assessed.
Main Results:
- 6-TG significantly reduced EV71 mRNA, VP1 protein, and viral production in HT-29 cells.
- 6-TG demonstrated a high selectivity index (SI > 2150.1) against EV71, surpassing ribavirin.
- 6-TG inhibited EV71 replication by decreasing BIRC3 expression and attenuating BIRC3-mediated autophagy.
Conclusions:
- 6-TG exhibits significant in vitro antiviral activity against EV71 infection.
- 6-TG prevents EV71-induced autophagy by reducing BIRC3 expression.
- 6-TG shows promise as a potential therapeutic agent for EV71-associated HFMD.

