Dissertation/Thesis Abstract

Structure-Based Approach Toward the Development of a Zika Methyltransferase Inhibitor
by Kim, Junghwan, M.S., Icahn School of Medicine at Mount Sinai, 2020, 56; 27834083
Abstract (Summary)

Zika virus (ZIKV) is a flavivirus that can cause microcephaly in newborns and Guillain-Barré syndrome (GBS) in adults. Recent ZIKV outbreaks from 2007 to 2018 have focused major attention on the virus, with WHO declaring it as Public Health Emergency of International Concern in 2016. Yet, there is no effective treatment option for a ZIKV infection and thus an antiviral is urgently needed. In this study, derivatives of the S-adenosylmethionine (SAM) were identified as potential inhibitors of the ZIKV NS5-Methyltransferase (NS5-MTase), a protein domain essential to the viral life cycle. Using structure-based drug design (SBDD), we explore the implications of structural variety of SAM derivatives on their binding to and disruption of the NS5-MTase. Following isothermal titration calorimetry and crystallography, we suggest viable candidate compounds for further studies.

Indexing (document details)
Advisor: Aggarwal, Aneel K., Jain, Rinku
Commitee: Moran, Thomas M., Zhou, Ming-Ming
School: Icahn School of Medicine at Mount Sinai
Department: Pharmacology and System Biology
School Location: United States -- New York
Source: MAI 81/10(E), Masters Abstracts International
Source Type: DISSERTATION
Subjects: Pharmacology, Biophysics, Virology
Keywords: Crystallography, Fast Protein Liquid Chromatography, Isothermal Titration Calorimetry, Methyltransferase, S-Adenosylmethionine, Zika Virus
Publication Number: 27834083
ISBN: 9798607318550
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