scholarly journals Delving into Zika virus structural dynamics – a closer look at NS3 helicase loop flexibility and its role in drug discovery

RSC Advances ◽  
2017 ◽  
Vol 7 (36) ◽  
pp. 22133-22144 ◽  
Author(s):  
Pritika Ramharack ◽  
Sofiat Oguntade ◽  
Mahmoud E. S. Soliman
Keyword(s):  
Drug Discovery ◽  
Structural Dynamics ◽  
Zika Virus ◽  
Potent Inhibitor ◽  
Structural Alterations ◽  
Loop Flexibility

This study demonstrates the structural alterations in the P-loop of ZIKV helicase subsequent to binding of potent inhibitor, NITD008.

In silico approaches to Zika virus drug discovery

2018 ◽  
Vol 13 (9) ◽  
pp. 825-835 ◽  
Author(s):  
Alessandro Sinigaglia ◽  
Silvia Riccetti ◽  
Marta Trevisan ◽  
Luisa Barzon
Keyword(s):  
Drug Discovery ◽  
Zika Virus ◽  
In Silico

scholarly journals Zika Virus Replicons for Drug Discovery

EBioMedicine ◽  
2016 ◽  
Vol 12 ◽  
pp. 156-160 ◽  
Author(s):  
Xuping Xie ◽  
Jing Zou ◽  
Chao Shan ◽  
Yujiao Yang ◽  
Dieudonné Buh Kum ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Zika Virus

scholarly journals Structural biology and drug discovery targeting Zika virus proteins

2018 ◽  
Vol WCP2018 (0) ◽  
pp. SY28-2
Author(s):  
Glaucius Oliva ◽  
Andre S. Godoy ◽  
Ketlyn I. Z.. Oliveira ◽  
Nathalya C. M. R. Mesquita ◽  
Gustavo M. A. Lima ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Structural Biology ◽  
Zika Virus ◽  
Virus Proteins

Structural dynamics and allostery of Rab proteins: strategies for drug discovery and design

2020 ◽  
Author(s):  
Ammu Prasanna Kumar ◽  
Chandra S Verma ◽  
Suryani Lukman
Keyword(s):  
Drug Discovery ◽  
Computational Methods ◽  
Structural Dynamics ◽  
Binding Sites ◽  
Structural Data ◽  
Extraction Methods ◽  
Rab Proteins ◽  
Nucleotide Binding Sites ◽  
Using Data ◽  
Guanosine Triphosphatase

Abstract Rab proteins represent the largest family of the Rab superfamily guanosine triphosphatase (GTPase). Aberrant human Rab proteins are associated with multiple diseases, including cancers and neurological disorders. Rab subfamily members display subtle conformational variations that render specificity in their physiological functions and can be targeted for subfamily-specific drug design. However, drug discovery efforts have not focused much on targeting Rab allosteric non-nucleotide binding sites which are subjected to less evolutionary pressures to be conserved, hence are likely to offer subfamily specificity and may be less prone to undesirable off-target interactions and side effects. To discover druggable allosteric binding sites, Rab structural dynamics need to be first incorporated using multiple experimentally and computationally obtained structures. The high-dimensional structural data may necessitate feature extraction methods to identify manageable representative structures for subsequent analyses. We have detailed state-of-the-art computational methods to (i) identify binding sites using data on sequence, shape, energy, etc., (ii) determine the allosteric nature of these binding sites based on structural ensembles, residue networks and correlated motions and (iii) identify small molecule binders through structure- and ligand-based virtual screening. To benefit future studies for targeting Rab allosteric sites, we herein detail a refined workflow comprising multiple available computational methods, which have been successfully used alone or in combinations. This workflow is also applicable for drug discovery efforts targeting other medically important proteins. Depending on the structural dynamics of proteins of interest, researchers can select suitable strategies for allosteric drug discovery and design, from the resources of computational methods and tools enlisted in the workflow.

scholarly journals Adenosine Analog NITD008 Is a Potent Inhibitor of Zika Virus

2016 ◽  
Vol 3 (4) ◽  
Author(s):  
Yong-Qiang Deng ◽  
Na-Na Zhang ◽  
Chun-Feng Li ◽  
Min Tian ◽  
Jia-Nan Hao ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Potent Inhibitor ◽  
Antiviral Drug ◽  
Clinical Manifestations ◽  
Drug Screen ◽  
Adenosine Analog

Abstract The ongoing Zika virus (ZIKV) outbreaks have raised global concerns due to its unexpected clinical manifestations. Antiviral development is of high priority in response to the ZIKV emergency. In this study, we report that an adenosine analog NITD008 has potent in vitro and in vivo antiviral activity against ZIKV. The compound can effectively inhibit the historical and contemporary ZIKV strains in cultures as well as significantly reduce viremia and prevent mortality in A129 mice. Our results have demonstrated that NITD008 is potent inhibitor of ZIKV and can be used as reference inhibitor for future ZIKV antiviral drug screen and discovery.

Zika virus drug targets: a missing link in drug design and discovery – a route map to fill the gap

RSC Advances ◽  
2016 ◽  
Vol 6 (73) ◽  
pp. 68719-68731 ◽  
Author(s):  
Pritika Ramharack ◽  
Mahmoud E. S. Soliman
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Viral Replication ◽  
Zika Virus ◽  
In Silico ◽  
Drug Targets ◽  
Missing Link ◽  
Potential Inhibitors

This review depicts anin silicoroute map for ZIKV drug discovery, thus revealing novel potential inhibitors of viral replication.

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