Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening

Area of Science:

• Ophthalmology
• Virology
• Cell Biology

Background:

• Understanding SARS-CoV-2 transmission is crucial for controlling the COVID-19 pandemic.
• The ocular surface's role in SARS-CoV-2 infection requires further investigation.
• Identifying effective antiviral therapies remains a global health priority.

Purpose of the Study:

• To investigate SARS-CoV-2 infection of ocular surface epithelial cells.
• To establish a novel cell model for studying ocular viral infections.
• To screen for potential antiviral drugs using the developed ocular cell model.

Main Methods:

• Infection of ocular surface limbal epithelial cells with SARS-CoV-2.
• Analysis of viral entry and replication mechanisms, including receptor dependence (ACE2, TMPRSS2).
• Screening of natural product libraries for antiviral activity against SARS-CoV-2 in the ocular model.

Main Results:

• SARS-CoV-2 specifically infects ocular surface limbal epithelial cells, not other ocular regions.
• Viral entry and replication are dependent on ACE2, TMPRSS2, and other receptors.
• Infection induced mild cytopathic effects (CPE) and interleukin-6 (IL-6) secretion, correlating with conjunctivitis symptoms.
• Two natural product libraries yielded several previously unreported antiviral compounds.
• Established an effective cell model for drug screening and mechanistic studies of ocular SARS-CoV-2 infection.

Conclusions:

• The ocular surface limbal epithelium is a susceptible site for SARS-CoV-2 infection.
• The developed limbal cell model is suitable for studying COVID-19 ocular manifestations and for antiviral drug discovery.
• Findings highlight commonalities between systemic COVID-19 and ocular SARS-CoV-2 infections, aiding therapeutic development.