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Find video protocols related to scientific articles indexed in Pubmed.
Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus.
Bioorg. Med. Chem. Lett.
PUBLISHED: 06-28-2013
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The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication.
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A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico.
Virol. J.
PUBLISHED: 01-28-2013
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Pandemic type A (H1N1) influenza arose in early 2009, probably in Mexico and the United States, and reappeared in North America in September for seven more months. An amino acid substitution in the hemagglutinin (HA), D222G, has been reported in a significant proportion of patients with a severe and fatal outcome. We studied the prevalence of HA222 substitutions in patients in Mexico during the second wave and its association with clinical outcome and pathogenicity in a mouse model.
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Synthesis and preclinical evaluation of a new C-6 alkylated pyrimidine derivative as a PET imaging agent for HSV1-tk gene expression.
Am J Nucl Med Mol Imaging
PUBLISHED: 01-05-2013
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[(18)F]FHOMP (6-((1-[(18)F]-fluoro-3-hydroxypropan-2-yloxy)methyl)-5-methylpyrimidine-2,4(1H,3H)-dione), a C-6 substituted pyrimidine derivative, has been synthesized and evaluated as a potential PET agent for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression. [(18)F]FHOMP was prepared by the reaction of the tosylated precursor with tetrabutylammonium [(18)F]-fluoride followed by acidic cleavage of the protecting groups. In vitro cell accumulation of [(18)F]FHOMP and [(18)F]FHBG (reference) was studied with HSV1-tk transfected HEK293 (HEK293TK+) cells. Small animal PET and biodistribution studies were performed with HEK293TK+ xenograft-bearing nude mice. The role of equilibrative nucleoside transporter 1 (ENT1) in the transport and uptake of [(18)F] FHOMP was also examined in nude mice after treatment with ENT1 inhibitor nitrobenzylmercaptopurine ribonucleoside phosphate (NBMPR-P). [(18)F]FHOMP was obtained in a radiochemical yield of ~25% (decay corrected) and the radiochemical purity was greater than 95%. The uptake of [(18)F]FHOMP in HSV1-TK containing HEK293TK+ cells was 52 times (at 30 min) and 244 times (at 180 min) higher than in control HEK293 cells. The uptake ratios between HEK293TK+ and HEK293 control cells for [(18)F]FHBG were significantly lower i.e. 5 (at 30 min) and 81 (240 min). In vivo, [(18)F]FHOMP accumulated to a similar extend in HEK293TK+ xenografts as [(18)F]FHBG but with a higher general background. Blocking of ENT1 reduced [(18)F]FHOMP uptake into brain from a standardized uptake value (SUV) of 0.10±0.01 to 0.06±0.02, but did not reduce the general background signal in PET. Although [(18)F]FHOMP does not outperform [(18)F]FHBG in its in vivo performance, this novel C-6 pyrimidine derivative may be a useful probe for monitoring HSV1-tk gene expression in vivo.
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Synthesis and evaluation of a C-6 alkylated pyrimidine derivative for the in vivo imaging of HSV1-TK gene expression.
Nucl. Med. Biol.
PUBLISHED: 05-17-2011
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We report on the synthesis, radiolabeling, in vitro and in vivo characterization of N-Me-[(18)F]FHBT (6-(3-[(18)F]fluoro-2-(hydroxymethyl)propyl)-1,5-dimethylpyrimidin-2,4(1H,3H)-dione), a C-6-substituted N-1-methylated pyrimidine derivative as a reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-TK) expression.
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Identification of high-affinity PB1-derived peptides with enhanced affinity to the PA protein of influenza A virus polymerase.
Antimicrob. Agents Chemother.
PUBLISHED: 12-06-2010
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The influenza A virus polymerase complex, consisting of the subunits PB1, PB2, and PA, represents a promising target for the development of new antiviral drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between PA and PB1 using peptides derived from the extreme N terminus of PB1 (amino acids [aa] 1 to 15), comprising the PA-binding domain of PB1. To increase the binding affinity of these peptides, we performed a systematic structure-affinity relationship analysis. Alanine and aspartic acid scans revealed that almost all amino acids in the core binding region (aa 5 to 11) are indispensable for PA binding. Using a library of immobilized peptides representing all possible single amino acid substitutions, we were able to identify amino acid positions outside the core PA-binding region (aa 1, 3, 12, 14, and 15) that are variable and can be replaced by affinity-enhancing residues. Surface plasmon resonance binding studies revealed that combination of several affinity-enhancing mutations led to an additive effect. Thus, the feasibility to enhance the PA-binding affinity presents an intriguing possibility to increase antiviral activity of the PB1-derived peptide and one step forward in the development of an antiviral drug against influenza A viruses.
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Identification of a PA-binding peptide with inhibitory activity against influenza A and B virus replication.
PLoS ONE
PUBLISHED: 07-31-2009
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There is an urgent need for new drugs against influenza type A and B viruses due to incomplete protection by vaccines and the emergence of resistance to current antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2 and PA subunits, represents a promising target for the development of new drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between the PB1 and PA subunits of the polymerase complex of influenza A virus using a small peptide derived from the PA-binding domain of PB1. However, this influenza A virus-derived peptide did not affect influenza B virus polymerase activity. Here we report that the PA-binding domain of the polymerase subunit PB1 of influenza A and B viruses is highly conserved and that mutual amino acid exchange shows that they cannot be functionally exchanged with each other. Based on phylogenetic analysis and a novel biochemical ELISA-based screening approach, we were able to identify an influenza A-derived peptide with a single influenza B-specific amino acid substitution which efficiently binds to PA of both virus types. This dual-binding peptide blocked the viral polymerase activity and growth of both virus types. Our findings provide proof of principle that protein-protein interaction inhibitors can be generated against influenza A and B viruses. Furthermore, this dual-binding peptide, combined with our novel screening method, is a promising platform to identify new antiviral lead compounds.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.