Abstract
Analogues of the natural product cyclosporine A (CsA) were developed and assessed as antivirals against infection of hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). An analogue termed 27A exhibits potent inhibition of HBV/HDV infection by specifically blocking viral engagement to its cellular receptor NTCP, while it lacks immunosuppressive activity found in natural CsA. Intraperitoneal injection or oral intake of 27A protects HDV-susceptible mouse model from HDV infection. 27A serves as a promising lead for the development of novel anti-HDV/HBV agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Antiviral Agents / administration & dosage
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use*
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Cyclosporine / administration & dosage
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Cyclosporine / pharmacology
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Cyclosporine / therapeutic use*
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Drug Design
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Drug Evaluation, Preclinical
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Hep G2 Cells
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Hepatitis B / drug therapy*
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Hepatitis B / physiopathology
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Hepatitis D / drug therapy*
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Hepatitis D / physiopathology
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Humans
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Mice
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Mice, Inbred C57BL
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Organic Anion Transporters, Sodium-Dependent / physiology*
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Symporters / physiology*
Substances
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Antiviral Agents
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Organic Anion Transporters, Sodium-Dependent
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Symporters
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sodium-bile acid cotransporter
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Cyclosporine