Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye

Area of Science:

• Ophthalmology
• Virology
• Immunology

Background:

• The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitates effective treatments.
• The eye serves as a potential entry point for SARS-CoV-2 infection.
• Understanding cellular mechanisms of viral entry is crucial for developing countermeasures.

Approach:

• Utilized an in vivo rat model of corneal inflammation and human corneal epithelial cells (HCEC) challenged with IFNγ.
• Investigated the blockade of the SARS-CoV-2 spike (S) protein's receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2).
• Assessed the effects of lipid mediators, specifically Elovanoid (ELV)-N32 and Resolvin D6-isomer (RvD6i), on cellular receptors and viral binding.

Key Points:

• Lipid mediators ELV-N32 and RvD6i consistently reduced ACE2 receptor, furin, and integrin expression in damaged corneas and IFNγ-stimulated HCEC.
• These lipid treatments decreased the binding of the spike RBD to the cells.
• The lipid mediators also attenuated the expression of pro-inflammatory cytokines involved in cytokine storm, hyper-inflammation, and senescence.

Conclusions:

• Lipid mediators demonstrate potential therapeutic value against SARS-CoV-2.
• These compounds counteract viral attachment and entry into ocular and other cells.
• The findings suggest novel therapeutic avenues for managing COVID-19 by targeting viral entry and associated inflammatory responses.