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

被引:1
作者
Xiao, Yu [1 ,4 ]
Wang, Ling [3 ]
Li, Shi-xu [3 ]
Fang, Shi-song [5 ]
Luo, Fan [2 ]
Chen, Shu-liang [2 ]
Zou, Xuan [5 ,6 ]
Ye, Lin [3 ]
Hou, Wei [1 ,2 ,7 ]
机构
[1] Wuhan Univ, Shenzhen Res Inst, Shenzhen 518057, Guangdong, Peoples R China
[2] Wuhan Univ, Inst Med Virol, Sch Basic Med Sci, State Key Lab Virol, Wuhan 430071, Hubei Province, Peoples R China
[3] Shenzhen Eye Hosp, 18 Zetian Rd, Shenzhen 518040, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 7, Dept Clin Lab, Shenzhen 518107, Peoples R China
[5] Shenzhen Ctr Dis Control & Prevent, Shenzhen 518055, Guangdong, Peoples R China
[6] Shenzhen Ctr Dis Control & Prevent, 8 Longyuan Rd, Shenzhen 518040, Guangdong, Peoples R China
[7] Wuhan Univ, Inst Med Virol, Sch Basic Med Sci, 185 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
关键词
COVID-19; Limbal; Cell model; Drug screening; SARS-COV-2; INFECTION; PROTEIN; ENTRY; ACE2;
D O I
10.1016/j.heliyon.2024.e30044
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 COVID19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.
引用
收藏
页数:14
相关论文
共 50 条
[1]   Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review [J].
Aiello, Francesco ;
Gallo Afflitto, Gabriele ;
Mancino, Raffaele ;
Li, Ji-Peng Olivia ;
Cesareo, Massimo ;
Giannini, Clarissa ;
Nucci, Carlo .
EYE, 2020, 34 (07) :1206-1211
[2]   Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein- Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 [J].
Bojadzic, Damir ;
Alcazar, Oscar ;
Chen, Jinshui ;
Chuang, Sung-Ting ;
Capcha, Jose M. Condor ;
Shehadeh, Lina A. ;
Buchwald, Peter .
ACS INFECTIOUS DISEASES, 2021, 7 (06) :1519-1534
[3]   SARS-CoV-2 infects an upper airway model derived from induced pluripotent stem cells [J].
Djidrovksi, Ivo ;
Georgiou, Maria ;
Hughes, Grant L. ;
Patterson, Edward I. ;
Casas-Sanchez, Aitor ;
Penington, Shaun H. ;
Biagini, Giancarlo A. ;
Moya-Molina, Marina ;
van den Bor, Jelle ;
Smit, Martine J. ;
Chung, Git ;
Lako, Majlinda ;
Armstrong, Lyle .
STEM CELLS, 2021, 39 (10) :1310-1321
[4]   SARS-CoV-2 infects human adult donor eyes and hESC-derived ocular epithelium [J].
Eriksen, Anne Z. ;
Moller, Rasmus ;
Makovoz, Bar ;
Uhl, Skyler A. ;
tenOever, Benjamin R. ;
Blenkinsop, Timothy A. .
CELL STEM CELL, 2021, 28 (07) :1205-+
[5]   SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain [J].
Fodoulian, Leon ;
Tuberosa, Joel ;
Rossier, Daniel ;
Boillat, Madlaina ;
Kan, Chenda ;
Pauli, Veronique ;
Egervari, Kristof ;
Lobrinus, Johannes A. ;
Landis, Basile N. ;
Carleton, Alan ;
Rodriguez, Ivan .
ISCIENCE, 2020, 23 (12)
[6]   IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine [J].
Furci, Fabiana ;
Murdaca, Giuseppe ;
Allegra, Alessandro ;
Gammeri, Luca ;
Senna, Gianenrico ;
Gangemi, Sebastiano .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (23)
[7]  
GBD 2021 Demographics Collaborators, 2024, Lancet, V403, P1989, DOI [10.1016/S0140-6736(24)00476-8, DOI 10.1016/S0140-6736(24)00476-8]
[8]   Stability and transmissibility of SARS-CoV-2 in the environment [J].
Geng, Yansheng ;
Wang, Youchun .
JOURNAL OF MEDICAL VIROLOGY, 2023, 95 (01)
[9]   COVID-19 and the eye [J].
Gronbeck, Christian ;
Grzybowski, Andrzej ;
Grant-Kels, Jane M. .
CLINICS IN DERMATOLOGY, 2024, 42 (01) :17-24
[10]   SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor [J].
Hoffmann, Markus ;
Kleine-Weber, Hannah ;
Schroeder, Simon ;
Krueger, Nadine ;
Herrler, Tanja ;
Erichsen, Sandra ;
Schiergens, Tobias S. ;
Herrler, Georg ;
Wu, Nai-Huei ;
Nitsche, Andreas ;
Mueller, Marcel A. ;
Drosten, Christian ;
Poehlmann, Stefan .
CELL, 2020, 181 (02) :271-+