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A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture

Overview of attention for article published in Virology Journal, January 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Good Attention Score compared to outputs of the same age and source (68th percentile)

Mentioned by

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6 tweeters
facebook
1 Facebook page

Citations

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27 Dimensions

Readers on

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106 Mendeley
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Title
A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture
Published in
Virology Journal, January 2015
DOI 10.1186/s12985-015-0248-x
Pubmed ID
Authors

Rajendra Raut, Hemalatha Beesetti, Poornima Tyagi, Ira Khanna, Swatantra K Jain, Variam U Jeankumar, Perumal Yogeeswari, Dharmarajan Sriram, Sathyamangalam Swaminathan

Abstract

Dengue has emerged as the most significant of arboviral diseases in the 21st century. It is endemic to >100 tropical and sub-tropical countries around the world placing an estimated 3.6 billion people at risk. It is caused by four genetically similar but antigenically distinct, serotypes of dengue viruses. There is neither a vaccine to prevent nor a drug to treat dengue infections, at the present time. The major objective of this work was to explore the possibility of identifying a small molecule inhibitor of the dengue virus protease and assessing its ability to suppress viral replication in cultured cells. We cloned, expressed and purified recombinant dengue virus type 2 protease. Using an optimized and validated fluorogenic peptide substrate cleavage assay to monitor the activity of this cloned dengue protease we randomly screened ~1000 small molecules from an 'in-house' library to identify potential dengue protease inhibitors. A benzimidazole derivative, named MB21, was found to be the most potent in inhibiting the cloned protease (IC50 = 5.95 μM). In silico docking analysis indicated that MB21 binds to the protease in the vicinity of the active site. Analysis of kinetic parameters of the enzyme reaction suggested that MB21 presumably functions as a mixed type inhibitor. Significantly, this molecule identified as an inhibitor of dengue type 2 protease was also effective in inhibiting each one of the four serotypes of dengue viruses in infected cells in culture, based on analysis of viral antigen synthesis and infectious virus production. Interestingly, MB21 did not manifest any discernible cytotoxicity. This work strengthens the notion that a single drug molecule can be effective against all four dengue virus serotypes. The molecule MB21 could be a potential candidate for 'hit-to-lead' optimization, and may pave the way towards developing a pan-dengue virus antiviral drug.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Indonesia 1 <1%
United Kingdom 1 <1%
Unknown 104 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 19%
Student > Bachelor 17 16%
Student > Master 15 14%
Student > Ph. D. Student 14 13%
Other 5 5%
Other 16 15%
Unknown 19 18%
Readers by discipline Count As %
Chemistry 21 20%
Biochemistry, Genetics and Molecular Biology 17 16%
Agricultural and Biological Sciences 16 15%
Immunology and Microbiology 9 8%
Pharmacology, Toxicology and Pharmaceutical Science 5 5%
Other 13 12%
Unknown 25 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 22 April 2016.
All research outputs
#2,015,689
of 8,974,298 outputs
Outputs from Virology Journal
#276
of 1,771 outputs
Outputs of similar age
#60,580
of 245,201 outputs
Outputs of similar age from Virology Journal
#15
of 54 outputs
Altmetric has tracked 8,974,298 research outputs across all sources so far. Compared to these this one has done well and is in the 77th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,771 research outputs from this source. They receive a mean Attention Score of 3.5. This one has done well, scoring higher than 84% of its peers.
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 245,201 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 54 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.