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Oxysterole-binding protein targeted by SARS-CoV-2 viral proteins regulates coronavirus replication

Yue Ma-Lauer1,2, Pengyuan Li1,2, Daniela Niemeyer3,4

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

Frontiers in Cellular and Infection Microbiology
|August 9, 2024
PubMed
Abstract

Insights

Oxysterol-binding protein (OSBP) promotes coronavirus replication. A new compound, ZJ-1, targets OSBP, reducing viral levels and showing antiviral effects against SARS-CoV-2 and other coronaviruses.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxysterol-binding protein (OSBP) is essential for lipid transport between cellular organelles.
  • The role of OSBP in coronavirus replication, including SARS-CoV-2, is not well understood.
  • Understanding OSBP's function in viral replication is critical for developing new antiviral strategies.

Purpose of the Study:

  • To investigate the role of OSBP in coronavirus replication.
  • To evaluate a novel OSBP-binding compound, ZJ-1, as a potential antiviral agent against coronaviruses.
  • To elucidate the molecular interactions between OSBP and SARS-CoV-2 proteins.

Main Methods:

  • Biochemical and cellular assays were employed to study OSBP interactions.
  • The effect of ZJ-1 on OSBP levels and viral replication was assessed.
  • Specific viral proteins and their interaction with OSBP and VAP-B were identified.

Main Results:

  • OSBP was found to positively regulate coronavirus replication.
  • ZJ-1 treatment decreased OSBP levels and demonstrated potent antiviral activity against multiple coronaviruses.
  • Interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) 3, 4, and 6 were identified, impacting double-membrane vesicle formation.
  • SARS-CoV-2 orf7a, orf7b, and orf3a were identified as OSBP targets, with OSBP stabilizing these proteins.

Conclusions:

  • OSBP plays a significant role in coronavirus replication and is a potential therapeutic target.
  • The OSBP-binding compound ZJ-1 shows promise as an antiviral agent against SARS-CoV-2 and other coronaviruses.
  • Targeting OSBP-mediated pathways offers a novel strategy for combating coronavirus infections.
Keywords:
Nsp3Nsp4Nsp6OSBPSARS-CoV-2VAP-Bcoronavirus

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