2. Academic Validation
  3. A novel SO2 probe inhibits lysophagy induced by Senecavirus A infection by promoting LAMP1 Cys375 sulfenylation

A novel SO2 probe inhibits lysophagy induced by Senecavirus A infection by promoting LAMP1 Cys375 sulfenylation

  • PLoS Pathog. 2026 Feb 5;22(2):e1013932. doi: 10.1371/journal.ppat.1013932.
Shuo Wang 1 2,  WenWen Han 1,  BaoXiang Zhao 3,  Ye Hong 1,  Jun Li 2,  JunYing Miao 1 4,  ZhaoMin Lin 5
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Development and Regeneration, School of Life Science, Shandong University, Qingdao, P.R. China.
  • 2 Key Laboratory of Livestock and Poultry Multi-omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, P.R. China.
  • 3 Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, P.R. China.
  • 4 State Key Laboratory of Microbial Technology (Microbial Technology Institute), Shandong University, Qingdao, P.R. China.
  • 5 Institute of Medical Science, the Second Hospital of Shandong University, Jinan, P.R. China.
PMID: 41642933 DOI: 10.1371/journal.ppat.1013932
Abstract

Lysophagy plays a key role in maintaining Autophagy homeostasis, but the induction and regulation mechanisms of lysophagy are not clear. In this study, we found that Senecavirus A (SVA) dramatically decreased lysosomal-associated membrane protein 1(LAMP1), significantly increased lysosomal permeability, and induced lysophagy. We demonstrated that the SO2 probe (2-(4-(dimethylamino-) phenyl)1,1, 3-trimethyl-1h-benzo [e] indole-3-ium, DLC) could inhibited the degradation of LAMP1 and reduced lysophagy caused by SVA Infection. DLC directly binds to LAMP1, and enhanced sulfenylation modification of LAMP1 at Cys375 to inhibit non-lysine ubiquitination. Finally, we verified the Antiviral effects of DLC in cells and in BALB/c mice. Taken together, our study lays the foundation for the identification of SVA Infection targets and the development of Antiviral drugs in the future.

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