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  3. Exploring the therapeutic potential of HAPC in COVID-19-induced acute lung injury

Exploring the therapeutic potential of HAPC in COVID-19-induced acute lung injury

  • Phytomedicine. 2025 Apr:139:156563. doi: 10.1016/j.phymed.2025.156563.
Zhichen Pu 1,  Lingling Li 2,  Yan Zhang 3,  Yinping Shui 4,  Jun Liu 5,  Xiaohu Wang 6,  Xiaogan Jiang 7,  Liqin Zhang 8,  Hui Yang 9
Affiliations

Affiliations

  • 1 Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wuhu, Anhui 241001, China,; Drug Clinical Evaluation, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China.
  • 2 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China.
  • 3 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China.
  • 4 Wannan Medical College Wuhu 241001, Anhui, PR China.
  • 5 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China.
  • 6 Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 7 Department of Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China,. Electronic address: yjsicu@126.com.
  • 8 Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wuhu, Anhui 241001, China,; Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China,. Electronic address: lizh333333@aliyun.com.
  • 9 Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wuhu, Anhui 241001, China,; Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China,; Tissue bank of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: tjykdxyh0203@163.com.
PMID: 40023068 DOI: 10.1016/j.phymed.2025.156563
Abstract

Background: Acute lung injury (ALI) is one of the critical complications of coronavirus disease 2019 (COVID-19), which significantly impacts the survival of patients.

Purpose: In this study, we screened COVID-19-related target genes and identified and optimized potential drugs targeting these genes for the treatment of COVID-19.

Study design: In this study, bioinformatic analyses were conducted and subsequently identified and optimized potential drugs targeting these genes for the treatment of COVID-19 were carried out.

Methods: Firstly, we analyzed the targets gene in patients with COVID-19 using single-cell data analysis. We performed structural modifications on Chicoric acid (CA) and combined it with hyaluronic acid to enhance the targeted activity towards Cluster of differentiation 44 (CD44). Poly (sodium-p styrenesulfonate) (PSS) was used to form a PSS-coated CA+hyaluronic acid nanocomplex (HA-P). Subsequently, Lactobacillus murinus conidia cell wall (CW) was encapsulated to prepare PSS-coated CA + hyaluronic acid + Lactobacillus murinus conidia cell wall (HAPC) nanocomplexes.

Results: The expression of APPL1 expression in macrophage of COVID-19 patients was up-regulation. CA was found to bind to the APPL1 protein and inhibit its ubiquitination. HAPC effectively targeted ALI through the highly efficient interaction between CD44 and Hyaluronic acid (HA). HAPC alleviated the symptoms of ALI and restored epithelial function in mice with ALI. HAPC induced the Adaptor protein containing a pH domain, PTB domain and leucine zipper motif 1 (APPL1)/ liver kinase B1 (LKB1)/ AMP-activated protein kinase (AMPK) pathway by inactivating the NOD - like receptor protein 3 (NLRP3) pathway in ALI. CA interacted with the APPL1 protein and prevented its ubiquitination. HAPC facilitated the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway. It promoted the formation of LKB1 at GLU-67, ARG-72, ARG-314, ASP-316, and GLN-312 and APPL1 at ARG-106, ASP-115, LYS-124, ASN-119, and GLU-120.

Conclusion: Altogether, HAPC nanocomplexes exerted anti-inflammatory effects on ALI by promoting the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway, and may be one new therapeutic strategie for ALI.

Keywords

Acute lung injury; COVID-19; HAPC; Nanocomplexes; Therapeutic strategies.

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