Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain

Zika virus and members of the Flaviviridae family are re-emerging pathogens that pose a significant threat to public health. The lack of a vaccine and specific treatment of has resulted in a need for the design of therapeutic treatments to target specific parts of virus replication cycles. H...

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Main Author: Zhang, Denzel Xugeng
Other Authors: Julien Lescar
Format: Final Year Project (FYP)
Language:English
Published: Nanyang Technological University 2022
Subjects:
Online Access:https://hdl.handle.net/10356/157309
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author Zhang, Denzel Xugeng
author2 Julien Lescar
author_facet Julien Lescar
Zhang, Denzel Xugeng
author_sort Zhang, Denzel Xugeng
collection NTU
description Zika virus and members of the Flaviviridae family are re-emerging pathogens that pose a significant threat to public health. The lack of a vaccine and specific treatment of has resulted in a need for the design of therapeutic treatments to target specific parts of virus replication cycles. Here, the RNA dependent RNA Polymerase (RdRP) of Zika Virus was purified based on previously established protocols. Fluorescence-based alkaline phosphatase coupled polymerase assay (FAPA), was used to screen a library of 86 compounds generated to target the Zika Virus NS5 RdRP. Hit compounds identified were tested for dose-response inhibition. Finally, crystallization efforts were carried out in hopes of obtaining crystal structures of inhibitor compounds in complex with the Zika NS5 RdRp protein.
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spelling ntu-10356/1573092023-02-28T18:09:25Z Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain Zhang, Denzel Xugeng Julien Lescar School of Biological Sciences Nanyang Institute of Structural Biology Julien@ntu.edu.sg Science::Biological sciences Zika virus and members of the Flaviviridae family are re-emerging pathogens that pose a significant threat to public health. The lack of a vaccine and specific treatment of has resulted in a need for the design of therapeutic treatments to target specific parts of virus replication cycles. Here, the RNA dependent RNA Polymerase (RdRP) of Zika Virus was purified based on previously established protocols. Fluorescence-based alkaline phosphatase coupled polymerase assay (FAPA), was used to screen a library of 86 compounds generated to target the Zika Virus NS5 RdRP. Hit compounds identified were tested for dose-response inhibition. Finally, crystallization efforts were carried out in hopes of obtaining crystal structures of inhibitor compounds in complex with the Zika NS5 RdRp protein. Bachelor of Science in Biological Sciences 2022-05-13T07:42:26Z 2022-05-13T07:42:26Z 2022 Final Year Project (FYP) Zhang, D. X. (2022). Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/157309 https://hdl.handle.net/10356/157309 en application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences
Zhang, Denzel Xugeng
Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title_full Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title_fullStr Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title_full_unstemmed Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title_short Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain
title_sort investigating non nucleoside inhibitors targeting the zika virus non structural protein 5 ns5 rna dependent rna polymerase rdrp domain
topic Science::Biological sciences
url https://hdl.handle.net/10356/157309
work_keys_str_mv AT zhangdenzelxugeng investigatingnonnucleosideinhibitorstargetingthezikavirusnonstructuralprotein5ns5rnadependentrnapolymeraserdrpdomain