6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy

  • BMC Microbiol. 2025 Jan 29;25(1):53. doi: 10.1186/s12866-025-03752-8.
Qiao You  #  1 ,  Jing Wu  #  1  2 ,  Ruining Lyu  1 ,  Yurong Cai  3 ,  Na Jiang  1 ,  Ye Liu  4 ,  Fang Zhang  5 ,  Yating He  1 ,  Deyan Chen  6  7  8 ,  Zhiwei Wu  9  10  11
Affiliations
  • 1. Center for Public Health Research, Medical School of Nanjing University, Nanjing, China.
  • 2. Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.
  • 3. Ningxia Institute of Clinical Medicine, Central Laboratory, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.
  • 4. China Department of Ophthalmology, Tianjin First Central Hospital, Tianjin, China.
  • 5. Department of Burn and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
  • 6. Center for Public Health Research, Medical School of Nanjing University, Nanjing, China. [email protected].
  • 7. Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui, China. [email protected].
  • 8. Medical School of Nanjing University, Nanjing, 210093, China. [email protected].
  • 9. Center for Public Health Research, Medical School of Nanjing University, Nanjing, China. [email protected].
  • 10. State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China. [email protected].
  • 11. Medical School of Nanjing University, Nanjing, 210093, China. [email protected].
  • # Contributed equally.
PMID: 39881250 DOI: 10.1186/s12866-025-03752-8
Abstract

Background: Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), and can cause severe cerebral complications and even fatality in children younger than 5 years old. However, there is no specific medication for EV71 Infection in clinical practice. Our previous studies had identified the 6-thioguanine (6-TG), an FDA-approved Anticancer drug, as a potential Antiviral agent, but its anti-EV71 activity is largely unknown, therefore, we aim to explore the Antiviral effect of 6-TG on EV71.

Results: 6-TG significantly suppressed EV71 mRNA level, VP1 protein expression, and viral progeny production in HT-29 cells. In EV71-infected HT-29 cells, the 50% cytotoxicity concentration of 6-TG (CC50) was > 2000 µM and the 50% inhibitory concentration of 6-TG against EV71 (IC50) was 0.9302 µM. Interestingly, the selectivity index (SI) value of 6-TG against EV71 was > 2150.1, which was higher than the SI value (> 66.7) of ribavirin. Mechanistically, 6-TG treatment reduced the expression of baculoviral IAP repeat containing 3 (BIRC3), and further inhibited EV71 replication by attenuating BIRC3-mediated the complete Autophagy.

Conclusions: 6-TG exerted a significant inhibitory effect on EV71 Infection in vitro and prevented EV71-induced the complete Autophagy by decreasing BIRC3 expression. Our work provided a basis for the further development of 6-TG as a therapy for EV71-associated HFMD.

Keywords
6-thioguanine (6-TG); Autophagy; BIRC3; EV71.
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