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The non-vesicular cholesterol transporter GRAMD1C is a pan-coronavirus antiviral target

Zhelin Su1,2, Zhen Fu1,2, Yichen Yang1,2

  • 1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.

Plos Biology
|April 6, 2026
PubMed

Insights

GRAMD1C, a cholesterol transporter, is essential for coronaviruses replication. Inhibiting GRAMD1C shows broad-spectrum antiviral potential against diverse coronaviruses, including SARS-CoV-2.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Coronaviruses (CoVs) depend on host lipid metabolism for replication.
  • Specific host factors and pathways remain incompletely defined.

Purpose of the Study:

  • Identify host factors crucial for coronavirus replication.
  • Investigate the role of non-vesicular cholesterol transport in viral replication.

Main Methods:

  • Identified GRAMD1C as a key host factor for multiple CoV genera.
  • Utilized transmission electron microscopy (TEM) to analyze replication factories.
  • Performed domain rescue and inhibitor experiments.
  • Assessed viral replication in GRAMD1C-deficient and inhibitor-treated mice.

Main Results:

  • GRAMD1C is recruited to replication factories via interaction with viral nsp3 and nsp4.
  • GRAMD1C facilitates the formation of double-membrane vesicles (DMVs).
  • GRAMD1C's cholesterol transport activity is vital for viral replication.
  • GRAMD1C deficiency or inhibition reduces viral replication in vivo.

Conclusions:

  • GRAMD1C is a critical host factor for the replication of diverse coronaviruses.
  • Non-vesicular cholesterol transport is important for viral replication.
  • GRAMD1C represents a promising broad-spectrum antiviral target.

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