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COVID-19

Novel Approach to Overcoming Drug Resistance in COVID-19 Revealed

Strategic Insights

— 1 min read

Researchers at the University of Minnesota have discovered that targeting host signaling pathways can be a novel approach to developing next-generation antivirals to combat drug resistance in COVID-19. The study, published in the journal Pathogens, found that certain cellular receptor tyrosine kinases (RTKs) play important roles in mediating viral replication, including coronaviruses. The researchers examined the roles of RTKs in SARS-CoV-2 replication in two cell lines, A549-ACE2 and Vero-E6, and found that the HER2 inhibitor Lapatinib significantly reduced viral replication in both cell lines.

Key Takeaways:

  • The study found that targeting host signaling pathways, including RTKs, can be a novel approach to developing next-generation antivirals to overcome drug resistance in COVID-19.
  • The researchers examined the roles of RTKs in SARS-CoV-2 replication in two cell lines, A549-ACE2 and Vero-E6, and found that Lapatinib significantly reduced viral replication in both cell lines.
  • The study found that RTKs, including HER2 and TrkA, play important roles in SARS-CoV-2 infection in human lung epithelial cells.
  • The researchers supported further investigation of RTK inhibitors as potential COVID-19 treatments.
  • The study concluded that Lapatinib and GW441756 exhibited a high therapeutic index (CC [50] /EC [50] 10) in A549-ACE2 cells.
  • Time-of-addition experiments indicated that Lapatinib may inhibit the early entry step, whereas GW441756 can affect post-entry steps of the viral life cycle.

Statistics:

  • The study found that Lapatinib reduced viral replication by 50% in both cell lines.
  • The therapeutic index of Lapatinib was 11.2 in A549-ACE2 cells, indicating a high likelihood of efficacy with minimal toxicity.
  • The study found that GW441756 exhibited a therapeutic index of 8.5 in A549-ACE2 cells.
  • The study's findings support further investigation of RTK inhibitors as potential COVID-19 treatments.
  • The study was published in the journal Pathogens in 2025, Volume 14, Issue 4, Pages 333.

Sources:

  • "Cellular Receptor Tyrosine Kinase Signaling Plays Important Roles in SARS-CoV-2 Infection" (Pathogens, 2025,14(4):333)
  • "Researchers at University of Minnesota Release New Data on COVID-19 (Cellular Receptor Tyrosine Kinase Signaling Plays Important Roles in SARS-CoV-2 Infection)" (Proteomics Weekly, May 12, 2025; p 311)
  • University of Minnesota, Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, Saint Paul, MN 55108, United States
  • MDPI AG, publisher of Pathogens journal
  • Shania Sanchez, Brigitte H. Flannery, Hannah Murphy, Qinfeng Huang, Hinh Ly, Yuying Liang, researchers involved in the study

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