2. Academic Validation
  3. 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy

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

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. chendeyan@nju.edu.cn.
  • 7 Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui, China. chendeyan@nju.edu.cn.
  • 8 Medical School of Nanjing University, Nanjing, 210093, China. chendeyan@nju.edu.cn.
  • 9 Center for Public Health Research, Medical School of Nanjing University, Nanjing, China. wzhw@nju.edu.cn.
  • 10 State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China. wzhw@nju.edu.cn.
  • 11 Medical School of Nanjing University, Nanjing, 210093, China. wzhw@nju.edu.cn.
  • # 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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