Abstract |
The adamantanes are a class of anti- influenza drugs that inhibit the M2 ion channel of the influenza A virus. However recently, the clinical effectiveness of these drugs has been called into question due to the emergence of adamantane-insensitive A/M2 mutants. Although we previously reported (1R,2R,3R,5S)-3-pinanamine 3 as a novel inhibitor of the wild type influenza A virus M2 protein (WT A/M2), limited inhibition was found for adamantane-resistant M2 mutants. In this study, we explored whether newly synthesized pinanamine derivatives were capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants. Several imidazole and guanazole derivatives of pinanamine were found to inhibit WT A/M2 to a comparable degree as amantadine and one of these compounds 12 exhibits weak inhibition of A/M2-S31N mutant and it is marginally more effective in inhibiting S31NM2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.
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Authors | Xin Zhao, Yanling Jie, Matthew R Rosenberg, Junting Wan, Shaogao Zeng, Wei Cui, Yiping Xiao, Zhiyuan Li, Zhengchao Tu, Marco G Casarotto, Wenhui Hu |
Journal | Antiviral research
(Antiviral Res)
Vol. 96
Issue 2
Pg. 91-9
(Nov 2012)
ISSN: 1872-9096 [Electronic] Netherlands |
PMID | 22982118
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier B.V. All rights reserved. |
Chemical References |
- Antiviral Agents
- Ion Channels
- M2 protein, Influenza A virus
- Viral Matrix Proteins
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Topics |
- Animals
- Antiviral Agents
(chemical synthesis, chemistry, isolation & purification, pharmacology)
- Cell Line
- Humans
- Influenza A virus
(drug effects)
- Ion Channels
(antagonists & inhibitors)
- Microbial Sensitivity Tests
- Molecular Structure
- Viral Matrix Proteins
(antagonists & inhibitors)
- Viral Plaque Assay
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