@article{4446bff8c0404c85b039bb4059b324f9,
title = "CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry",
abstract = "The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about.",
keywords = "Cell biology, Virology",
author = "Heinl, {Elena Sofia} and Sebastian Lorenz and Barbara Schmidt and {Nasser M Laqtom}, Nouf and Mazzulli, {Joseph R.} and Laetitia Francelle and Yu, {Timothy W.} and Benjamin Greenberg and Stephan Storch and Ines Tegtmeier and Helga Othmen and Katja Maurer and Malin Steinfurth and Ralph Witzgall and Vladimir Milenkovic and Wetzel, {Christian H.} and Markus Reichold",
note = "Funding Information: Remdesivir was kindly provided by Dr. Eckhard Wiegrebe, pharmacy of the University Hospital Regensburg. We thank Anette Rohrhofer for excellent technical assistance. We acknowledge financial support through the pandemic responsiveness fund of The Bavarian Ministry of Science and Art . Funding Information: Remdesivir was kindly provided by Dr. Eckhard Wiegrebe, pharmacy of the University Hospital Regensburg. We thank Anette Rohrhofer for excellent technical assistance. We acknowledge financial support through the pandemic responsiveness fund of The Bavarian Ministry of Science and Art. E.S.H. conducted the GM1 measurements and the quantification of macropinocytosis on HEK293 cells; S.L. performed the experiments on cell migration and cell adhesion; B.S. did all infections with SARS-CoV-2, quantification of the viral load, and helped with designing SARS-CoV-2-related experiments; N.N.M.L. created the CLN7 knockout HEK293 cell line; J.R.M. and L.F. conducted the GM1 measurements on fibroblasts of patients with CLN7; T.W.Y. and B.G. provided the fibroblast cell lines from patients with CLN7; I.T. did most of the cell culture work and qPCR experiments; H.O. performed the electron microscopy studies including the sample preparation; K.M. and M.S. did the ACE2 receptor quantification; R.W. helped with interpreting the electron microscopic images; S.S. created and provided CLN7-deficient MEF cells; V.M. and C.H.W. were generating the plasmids and helped with questions concerning molecular biology; M.R. was designing the experiments and wrote the paper. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = oct,
day = "21",
doi = "10.1016/j.isci.2022.105082",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "10",
}