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Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening
Yu Xiao1,2, Ling Wang3, Shi-Xu Li3
1Shenzhen Research Institute, Wuhan University, Shenzhen 518057, Guangdong Province, China.
Abstract:
To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects ocular limbal epithelial cells, leading to conjunctivitis. This discovery establishes a new cell model for screening antiviral drugs against COVID-19.
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.
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