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Basic Characteristics of Mutations
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Mutation Site
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H274Y |
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Mutation Site Sentence
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Compound 16 displayed a significant decrease of viral titer when evaluated in the infectious assays with influenza virus H1N1 (A/Puerto Rico/8/1934) or H5N1 (A/Vietnam/1203/2004) strains and the oseltamivir-resistant strain with the most common H274Y mutation. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NA |
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Standardized Encoding Gene
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NA
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Genotype/Subtype
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H1N1 |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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Disease
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Influenza A
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Immune
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- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
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Clinical Information
|
- |
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Treatment
|
Oseltamivir |
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Location
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- |
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Literature Information
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|
PMID
|
32069052
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Title
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Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir
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Author
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Gaisina IN,Peet NP,Cheng H,Li P,Du R,Cui Q,Furlong K,Manicassamy B,Caffrey M,Thatcher GRJ,Rong L
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Journal
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Journal of medicinal chemistry
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Journal Info
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2020 Mar 26;63(6):3120-3130
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Abstract
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Vaccination is the most prevalent prophylactic means for controlling seasonal influenza infections. However, an effective vaccine usually takes at least 6 months to develop for the circulating strains. Therefore, new therapeutic options are needed for the acute treatment of influenza infections to control this virus and prevent epidemics/pandemics from developing. We have discovered fast-acting, orally bioavailable acylated 4-aminopiperidines with an effective mechanism of action targeting viral hemagglutinin (HA). Our data show that these compounds are potent entry inhibitors of influenza A viruses. We present docking studies that suggest an HA binding site for these inhibitors on H5N1. Compound 16 displayed a significant decrease of viral titer when evaluated in the infectious assays with influenza virus H1N1 (A/Puerto Rico/8/1934) or H5N1 (A/Vietnam/1203/2004) strains and the oseltamivir-resistant strain with the most common H274Y mutation. In addition, compound 16 showed significant synergistic activity with oseltamivir in vitro.
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Sequence Data
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-
|