A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still needed. In this study, human single chain variable fragments of antibody (scFvs) that bound to HCV NS3/4A protein were produced by phage display technology. The engineered scFvs were linked to nonaarginines (R9) for making them cell penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced from four different transformed E. coli clones had reduced HCV-RNA inside the cells and in the cell spent media, as well as fewer HCV foci in the cell monolayer compared to the transfected cells in culture medium alone. The transbodies-treated transfected cells also had up-expression of the genes coding for the host innate immune response, including TRIF, TRAF3, IRF3, IL-28B, and IFN-β. Computerized homology modeling and intermolecular docking predicted that the effective transbodies interacted with several critical residues of the NS3/4A protease, including those that form catalytic triads, oxyanion loop, and S1 and S6 pockets, as well as a zinc-binding site. Although insight into molecular mechanisms of the transbodies need further laboratory investigation, it can be deduced from the current data that the transbodies blocked the HCV NS3/4A protease activities, leading to the HCV replication inhibition and restoration of the virally suppressed host innate immunity. The engineered antibodies should be tested further for treatment of HCV infection either alone, in combination with current therapeutics, or in a mixture with their cognates specific to other HCV proteins.
Pharmacology, Toxicology and Pharmaceutical Science
2
11%
Medicine and Dentistry
1
6%
Other
1
6%
Unknown
4
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 September 2016.
All research outputs
#17,450,897
of 25,604,262 outputs
Outputs from Frontiers in immunology
#20,596
of 32,042 outputs
Outputs of similar age
#229,767
of 350,356 outputs
Outputs of similar age from Frontiers in immunology
#92
of 142 outputs
Altmetric has tracked 25,604,262 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 32,042 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 350,356 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 142 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
