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Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

Yiwei Zhang1, Zhengwei Duan1, Yonghao Guan1

  • 1Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Frontiers in Immunology
|June 7, 2023
PubMed

Insights

This study identifies three key genes (DDIT3, MAFF, PNRC1) common to Osteoarthritis and COVID-19, suggesting immune dysfunction as a shared pathway. Niclosamide, ciclopirox, and ticlopidine show potential for treating co-infected patients.

Area of Science:

  • Genetics and Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • Osteoarthritis (OA) and Corona Virus Disease 2019 (COVID-19) significantly impact patient health and quality of life, especially in the elderly.
  • The genetic links and shared pathogenesis between OA and COVID-19 remain largely unexplored.
  • Understanding these connections is crucial for developing targeted treatments for patients with both conditions.

Purpose of the Study:

  • To investigate the shared genetic pathogenesis between Osteoarthritis and COVID-19.
  • To identify key genes involved in the common pathways of OA and COVID-19.
  • To predict potential therapeutic drugs for patients suffering from both OA and SARS-CoV-2 infection.

Main Methods:

  • Utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis on public datasets (GEO database) for OA and COVID-19.
  • Applied the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to identify key genes and single-cell analysis for expression patterns.
  • Performed drug prediction and molecular docking using the Drug Signatures Database (DSigDB) and AutoDockTools.

Main Results:

  • Identified 26 common genes between OA and COVID-19, primarily linked to immune dysfunction.
  • Screened three key genes (DDIT3, MAFF, PNRC1) potentially involved in OA and COVID-19 pathogenesis, showing high expression in neutrophils.
  • Established a gene regulatory network and used binding energy estimation to identify potential drugs.

Conclusions:

  • Successfully identified DDIT3, MAFF, and PNRC1 as key genes with high diagnostic value for both OA and COVID-19.
  • Niclosamide, ciclopirox, and ticlopidine emerged as potential therapeutic agents for treating OA patients with SARS-CoV-2 infection.
  • The study provides a foundation for understanding the molecular mechanisms underlying co-infection and guides therapeutic strategies.
Abstract

Keywords:
COVID-19SARS-CoV-2 infectiondrug predictionosteoarthritissingle-cell analysis

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