CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

Area of Science:

• Immunology
• Virology
• Hematology

Background:

• Aberrant coagulation and thrombosis are hallmarks of severe COVID-19.
• The precise mechanisms driving these thrombotic events post-SARS-CoV-2 infection are not fully understood.

Purpose of the Study:

• To elucidate the role of SARS-CoV-2 envelope (E) protein in COVID-19-associated coagulation disorders.
• To identify molecular targets for mitigating E protein-induced thrombosis.

Main Methods:

• Measurement of serum SARS-CoV-2 E protein levels in COVID-19 patients.
• In vivo thrombosis models in mice using E protein administration.
• Protein pull-down assays and mass spectrometry to identify E protein binding partners.
• Platelet activation assays in human and mouse models.
• Pharmacological blockade and genetic deficiency studies of CD36 and p38 MAPK pathway.

Main Results:

• Serum E protein levels correlate with coagulation disorders in COVID-19 patients.
• Intravenous E protein administration induces thrombosis in mice.
• CD36 directly binds to the SARS-CoV-2 E protein.
• E protein binding to CD36 triggers platelet hyperactivation via the p38 MAPK-NF-κB pathway.
• Inhibition of CD36 or p38 significantly reduces E protein-induced platelet activation and thrombosis in vitro and in vivo.

Conclusions:

• The SARS-CoV-2 E protein plays a critical role in promoting platelet hyperactivity and thrombosis.
• The CD36-p38 axis is a key mediator of E protein-induced platelet activation.
• Targeting the CD36-p38 pathway presents a potential therapeutic strategy for managing COVID-19-related thrombotic complications.