TY  - JOUR
A1  - Sarukhanyan, Edita
A1  - Shityakov, Sergey
A1  - Dandekar, Thomas
T1  - In silico designed Axl receptor blocking drug candidates against Zika virus infection
JF  - ACS Omega
N2  - After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.
KW  - free energy
KW  - molecular docking
KW  - molecular dynamics
KW  - simulation
KW  - pharmacology
KW  - proteins
KW  - structure-activity relationship
KW  - viruses
KW  - Zika virus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176739
VL  - 3
IS  - 5
ER  - 
TY  - JOUR
A1  - Bencurova, Elena
A1  - Gupta, Shishir K.
A1  - Sarukhanyan, Edita
A1  - Dandekar, Thomas
T1  - Identification of antifungal targets based on computer modeling
JF  - Journal of Fungi
N2  - Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools.
KW  - Aspergillus
KW  - metabolic pathways
KW  - computational modelling
KW  - drug design
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197670
SN  - 2309-608X
VL  - 4
IS  - 3
ER  -