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LMP7 as a Target for Coronavirus Therapy: Inhibition by Ixazomib and Interaction with SARS-CoV-2 Proteins Nsp13 and

Yi Ru1,2, Yue Ma-Lauer1,2, Chengyu Xiang1,2

  • 1Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.

Pathogens (Basel, Switzerland)
|September 27, 2025
PubMed

Insights

Researchers identified Ixazomib and its analogs as potential antivirals by targeting the immunoproteasome subunit LMP7. This discovery offers new therapeutic strategies against human coronavirus infections.

Area of Science:

  • Virology
  • Immunology
  • Drug Discovery

Background:

  • Human coronaviruses have caused significant mortality through recurrent epidemics and pandemics.
  • There is an urgent need for novel antiviral drugs and therapeutic targets to combat coronavirus threats.

Purpose of the Study:

  • To screen for novel inhibitors of coronavirus replication.
  • To identify potential antiviral agents and therapeutic targets against human coronaviruses.

Main Methods:

  • Screening of a compound library to identify inhibitors.
  • Utilizing yeast two-hybrid assays and co-immunoprecipitation to study protein interactions.
  • Investigating the role of the immunoproteasome subunit LMP7 in viral replication through knockout studies.

Main Results:

  • Identified three lead compounds (Ixazomib and analogs) with potent antiviral activity and low cytotoxicity.
  • Demonstrated that these compounds inhibit LMP7, which is altered in SARS-CoV-2 infected cells.
  • Revealed interactions between LMP7 and viral proteins Nsp13 and Nsp16, with viral proteins disrupting LMP7 expression.
  • Showed that LMP7 knockout enhances viral replication, indicating its role in restricting infection.

Conclusions:

  • LMP7 is a novel therapeutic target for antiviral drug development.
  • Ixazomib and its analogs show promise as antiviral agents against current and future coronavirus threats.
Keywords:
IxazomibLMP7Nsp13Nsp16SARS-CoV-2immunoproteasome

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