Abstract
Recent research has shown that Coronavirus (CoV) replication depends on active immunophilin pathways. Here we demonstrate that the drug FK506 (Tacrolimus) inhibited strongly the growth of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E at low, non-cytotoxic concentrations in cell culture. As shown by plaque titration, qPCR, Luciferase- and green fluorescent protein (GFP) reporter gene expression, replication was diminished by several orders of magnitude. Knockdown of the cellular FK506-binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Caco-2 Cells
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Coronavirus 229E, Human / drug effects*
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Coronavirus 229E, Human / physiology
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Coronavirus Infections / genetics
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Coronavirus Infections / metabolism
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Coronavirus Infections / virology
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Coronavirus NL63, Human / drug effects*
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Coronavirus NL63, Human / physiology
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Humans
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Severe Acute Respiratory Syndrome / genetics
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Severe Acute Respiratory Syndrome / metabolism
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Severe Acute Respiratory Syndrome / virology
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Severe acute respiratory syndrome-related coronavirus / drug effects*
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Severe acute respiratory syndrome-related coronavirus / physiology
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Tacrolimus / pharmacology*
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Tacrolimus Binding Proteins / genetics
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Tacrolimus Binding Proteins / metabolism
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Virus Replication / drug effects*
Substances
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Tacrolimus Binding Proteins
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Tacrolimus