ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike...

Area of Science:

• Ophthalmology
• Virology
• Immunology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic necessitating effective treatments.
• The eye surface represents a potential entry route for SARS-CoV-2.
• There is a need to explore therapeutic strategies targeting viral attachment and entry.

Purpose of the Study:

• To investigate the potential of specific lipid mediators to block SARS-CoV-2 Spike (S) protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor.
• To evaluate the effect of these lipid mediators on viral entry pathways in ocular models.
• To identify the impact of lipid mediators on inflammatory responses relevant to SARS-CoV-2 infection.

Main Methods:

• Utilized an in vivo rat model of corneal inflammation and human corneal epithelial cells (HCEC) challenged with IFNγ.
• Assessed the expression of ACE2, furin, and integrins following treatment with elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i).
• Measured the binding of SARS-CoV-2 Spike receptor-binding domain (RBD) to treated cells.
• Employed RNA-sequencing (RNA-seq) to analyze changes in gene expression, particularly pro-inflammatory cytokines.

Main Results:

• ELV-N32 and RvD6i significantly decreased the expression of ACE2, furin, and integrins in damaged corneas and IFNγ-stimulated HCEC.
• These lipid mediators reduced the binding of Spike RBD to the ocular surface models.
• RNA-seq analysis revealed that the lipid mediators attenuated the expression of pro-inflammatory cytokines involved in hyper-inflammation and senescence.

Conclusions:

• The studied lipid mediators demonstrate bioactivity against key SARS-CoV-2 entry factors on the ocular surface.
• ELV-N32 and RvD6i show promise in mitigating viral attachment and entry.
• These findings suggest potential therapeutic avenues for developing treatments against SARS-CoV-2 infection using these lipid mediators.