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Article ; Online: Lysosomal ion channels involved in cellular entry and uncoating of enveloped viruses: Implications for therapeutic strategies against SARS-CoV-2.

Zhao, Zhuangzhuang / Qin, Pan / Huang, Yao-Wei

Cell calcium

2021  Volume 94, Page(s) 102360

Abstract: ... knowledge of the effects of lysosomal ion channels on the cellular entry and uncoating of enveloped viruses ... With the ongoing outbreak of severe acute respiratory syndrome (SARS)-CoV-2, endolysosomal two-pore channels ... which may aid in development of novel therapies against emerging infectious diseases such as SARS-CoV-2. ...

Abstract Ion channels are necessary for correct lysosomal function including degradation of cargoes originating from endocytosis. Almost all enveloped viruses, including coronaviruses (CoVs), enter host cells via endocytosis, and do not escape endosomal compartments into the cytoplasm (via fusion with the endolysosomal membrane) unless the virus-encoded envelope proteins are cleaved by lysosomal proteases. With the ongoing outbreak of severe acute respiratory syndrome (SARS)-CoV-2, endolysosomal two-pore channels represent an exciting and emerging target for antiviral therapies. This review focuses on the latest knowledge of the effects of lysosomal ion channels on the cellular entry and uncoating of enveloped viruses, which may aid in development of novel therapies against emerging infectious diseases such as SARS-CoV-2.
MeSH term(s) Aminopyridines/pharmacology ; Aminopyridines/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/virology ; Drug Design ; Endocytosis ; Endosomes/metabolism ; Endosomes/virology ; Heterocyclic Compounds, 3-Ring/pharmacology ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Hydrazones/pharmacology ; Hydrazones/therapeutic use ; Ion Channels/classification ; Ion Channels/physiology ; Lysosomes/enzymology ; Lysosomes/metabolism ; Lysosomes/virology ; Models, Biological ; Morpholines/pharmacology ; Morpholines/therapeutic use ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; SARS-CoV-2/physiology ; Vacuolar Proton-Translocating ATPases/physiology ; Viral Envelope/physiology ; Virus Internalization/drug effects ; Virus Uncoating/drug effects
Chemical Substances 6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide ; Aminopyridines ; Antiviral Agents ; Heterocyclic Compounds, 3-Ring ; Hydrazones ; Ion Channels ; Morpholines ; Pyrimidines ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; apilimod (GFW2K84S4L)
Language English
Publishing date 2021-01-23
Publishing country Netherlands
Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID 757687-0
ISSN 1532-1991 ; 0143-4160
ISSN (online) 1532-1991
ISSN 0143-4160
DOI 10.1016/j.ceca.2021.102360
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