TY  - JOUR
AU  - Coronado, Monika Aparecida
AU  - Eberle, Raphael Josef
AU  - Bleffert, Nicole
AU  - Feuerstein, Sophie
AU  - Olivier, Danilo Silva
AU  - de Moraes, Fabio Rogerio
AU  - Willbold, Dieter
AU  - Arni, Raghuvir Krishnaswamy
TI  - Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition-
JO  - Antiviral research
VL  - 160
SN  - 0166-3542
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - FZJ-2018-07283
SP  - 118 - 125
PY  - 2018
AB  - Zika virus infection is the focus of much research due to the medical and social repercussions. Due the role of the viral NS2B/NS3 proteinase in maturation of the viral proteins, it had become an attractive antiviral target. Numerous investigations on viral epidemiology, structure and function analysis, vaccines, and therapeutic drugs have been conducted around the world. At present, no approved vaccine or even drugs have been reported. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified the polyanion suramin, an approved antiparasitic drug with antiviral properties, as a potential inhibitor of Zika virus complex NS2B/NS3 proteinase with IC50 of 47 μM. Using fluorescence spectroscopy results we could determine a kd value of 28 μM and had shown that the ligand does not affect the thermal stability of the protein. STD NMR spectroscopy experiments and molecular docking followed by molecular dynamics simulation identified the binding epitopes of the molecule and shows the mode of interaction, respectively. The computational analysis showed that suramin block the Ser135 residue and interact with the catalytically histidine residue.
LB  - PUB:(DE-HGF)16
C6  - pmid:30393012
UR  - <Go to ISI:>//WOS:000451936000014
DO  - DOI:10.1016/j.antiviral.2018.10.019
UR  - https://juser.fz-juelich.de/record/858397
ER  -