Abstract
This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76-118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC50 = 7.6 ± 2 µM) along with low toxicity (CC50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.
Keywords:
Antiviral; HFRS; Hantavirus; Isoindole; Terpene.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis
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Antiviral Agents / metabolism
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Antiviral Agents / pharmacology*
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Camphanes / chemical synthesis
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Camphanes / metabolism
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Camphanes / pharmacology*
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Capsid Proteins / metabolism
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Dogs
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Drug Design
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HEK293 Cells
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Hantaan virus / drug effects*
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Humans
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Hydrazones / chemical synthesis
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Hydrazones / metabolism
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Hydrazones / pharmacology*
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Isoindoles / chemical synthesis
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Isoindoles / metabolism
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Isoindoles / pharmacology*
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Madin Darby Canine Kidney Cells
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Microbial Sensitivity Tests
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Molecular Docking Simulation
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Norbornanes / chemical synthesis
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Norbornanes / metabolism
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Norbornanes / pharmacology*
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Protein Binding
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Viral Core Proteins / metabolism
Substances
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Antiviral Agents
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Camphanes
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Capsid Proteins
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Hydrazones
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Isoindoles
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Norbornanes
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Viral Core Proteins
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nucleocapsid protein, Hantaan virus
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fenchone
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norcamphor