Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening
Yu Xiao,
Ling Wang,
Shi-xu Li,
Shi-song Fang,
Fan Luo,
Shu-liang Chen,
Xuan Zou,
Lin Ye,
Wei Hou
Affiliations
Yu Xiao
Shenzhen Research Institute, Wuhan University, Shenzhen 518057, Guangdong Province, China; Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, China
Ling Wang
Shenzhen Eye Hospital, Shenzhen 518040, Guangdong Province, China
Shi-xu Li
Shenzhen Eye Hospital, Shenzhen 518040, Guangdong Province, China
Shi-song Fang
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong Province, China
Fan Luo
State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
Shu-liang Chen
State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
Xuan Zou
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong Province, China; Corresponding author. : Xuan Zou, Shenzhen Center for Disease Control and Prevention, 8 Longyuan Road, Nanshan District, Shenzhen 518040, Guangdong Province, China.
Shenzhen Research Institute, Wuhan University, Shenzhen 518057, Guangdong Province, China; State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China; Corresponding author. Hou Wei, Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Wuhan 430071, China.
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.
