PMID- 25847003
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20191113
IS  - 1875-6697 (Electronic)
IS  - 1573-4099 (Linking)
VI  - 10
IP  - 4
DP  - 2014
TI  - 3D Modeling of dengue virus NS4B and Chikungunya virus nsP4: identification of a 
      common drug target and designing a single antiviral inhibitor.
PG  - 361-73
AB  - Dengue and chikungunya virus infections are one of the major causes of morbidity 
      and mortality in tropical and sub-tropical regions of the world. These two 
      viruses belong to two different families with many similarities and 
      dissimilarities. Both are enveloped viruses and the mode of transmission is also 
      by the same mosquito species. Especially in case of symptom expression, there is 
      confusion between these two viruses. Reports indicate the overlapping endemic 
      areas and co-infections of both viruses in a single patient. The above factors 
      indicate that there is a need for developing a single drug/vaccine for both the 
      viruses. As a first report in this direction, we have used the bioinformatics 
      tools to identify a common target in both the viruses for a single inhibitor 
      molecule. Phylogenetic and distance based analyses using the nucleotide sequences 
      of arthropod and non-arthropod borne viruses indicated a common origin of 
      evolutionary point for mosquito borne viruses, irrespective of their families. 
      Similarly, the amino acid sequences of non-structural protein-4B (NS4B) of dengue 
      virus and non-structural protein-P4 (nsP4) of chikungunya virus showed a common 
      evolutionary origin. Modeled and superimposed 3D-structures of above two proteins 
      showed a common alpha helix. Virtual screening of selected molecules was done to 
      identify the molecules which can bind to the identified common helix and found 
      that N-(p-tolylmethyl)-3-[(3-pyridylmethylamino)methyl]benzamide (TPB) has 
      significant binding characteristics to the common helix. Molecular simulations 
      indicated that both the protein-TPB complexes were stable. Therefore, we propose 
      that TPB or its analogues could act as antiviral agents against both the viruses.
FAU - Satheesh, Garisekurthi
AU  - Satheesh G
FAU - Prabhu, Nagu P
AU  - Prabhu NP
FAU - Venkataramana, Musturi
AU  - Venkataramana M
AD  - Department of Biotechnology and Bioinformatics, School of Life Sciences, 
      University of Hyderabad, Hyderabad, Andhra Pradesh, PIN-500046, India. 
      mvrsl@uohyd.ernet.in.
LA  - eng
PT  - Journal Article
PL  - United Arab Emirates
TA  - Curr Comput Aided Drug Des
JT  - Current computer-aided drug design
JID - 101265750
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzamides)
RN  - 0 (Pyridines)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Antiviral Agents/*chemistry/*pharmacology
MH  - Benzamides/*pharmacology
MH  - Binding Sites
MH  - Chikungunya virus/*chemistry
MH  - Dengue Virus/*chemistry
MH  - *Drug Design
MH  - *Models, Molecular
MH  - Pyridines/*pharmacology
MH  - Viral Nonstructural Proteins/*antagonists & inhibitors/*chemistry
EDAT- 2015/04/08 06:00
MHDA- 2015/11/17 06:00
CRDT- 2015/04/08 06:00
PHST- 2014/04/09 00:00 [received]
PHST- 2014/04/12 00:00 [revised]
PHST- 2014/07/02 00:00 [accepted]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
AID - CAD-EPUB-66393 [pii]
AID - 10.2174/1573409911666150407161535 [doi]
PST - ppublish
SO  - Curr Comput Aided Drug Des. 2014;10(4):361-73. doi: 
      10.2174/1573409911666150407161535.