| Title |
Identification of covalent active site inhibitors of dengue virus protease
|
|---|---|
| Published in |
Drug Design, Development and Therapy, December 2015
|
| DOI | 10.2147/dddt.s94207 |
| Pubmed ID | |
| Authors |
Xiaoying Koh-Stenta, Joma Joy, Si Fang Wang, Perlyn Zekui Kwek, John Liang Kuan Wee, Kah Fei Wan, Shovanlal Gayen, Angela Shuyi Chen, CongBao Kang, May Ann Lee, Anders Poulsen, Subhash G Vasudevan, Jeffrey Hill, Kassoum Nacro |
| Abstract |
Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and protease-inhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 33% |
| United States | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 33% |
| Members of the public | 1 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 1% |
| Unknown | 66 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 19 | 28% |
| Researcher | 11 | 16% |
| Student > Master | 9 | 13% |
| Professor > Associate Professor | 6 | 9% |
| Student > Bachelor | 4 | 6% |
| Other | 12 | 18% |
| Unknown | 6 | 9% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 15 | 22% |
| Biochemistry, Genetics and Molecular Biology | 14 | 21% |
| Agricultural and Biological Sciences | 12 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 10% |
| Medicine and Dentistry | 3 | 4% |
| Other | 7 | 10% |
| Unknown | 9 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 18 December 2015.
All research outputs
#14,660,010
of 25,461,852 outputs
Outputs from Drug Design, Development and Therapy
#775
of 2,272 outputs
Outputs of similar age
#191,008
of 396,015 outputs
Outputs of similar age from Drug Design, Development and Therapy
#30
of 94 outputs
Altmetric has tracked 25,461,852 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,272 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 65% 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 396,015 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 94 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 67% of its contemporaries.