Nucleotide Substrate Specificity of Anti-Hepatitis C Virus Nucleoside Analogs for Human Mitochondrial RNA Polymerase-Reference-Cited by-同舟云学术

Nucleotide Substrate Specificity of Anti-Hepatitis C Virus Nucleoside Analogs for Human Mitochondrial RNA Polymerase

Published:2017-08 Issue:8 Volume:61 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Ehteshami Maryam¹,Zhou Longhu¹,Amiralaei Sheida¹,Shelton Jadd R.¹,Cho Jong Hyun¹,Zhang Hongwang¹,Li Hao¹,Lu Xiao¹,Ozturk Tugba¹,Stanton Richard¹,Amblard Franck¹,McBrayer Tamara R.²,Coats Steven J.²,Schinazi Raymond F.¹

Affiliation:

1. Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA

2. Cocrystal Pharma, Inc., Tucker, Georgia, USA

Abstract

ABSTRACT Nucleoside analog inhibitors (NAIs) are an important class of antiviral agents. Although highly effective, some NAIs with activity against hepatitis C virus (HCV) can cause toxicity, presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The in vitro nucleotide substrate specificity of POLRMT was studied in order to explore structure-activity relationships that can facilitate the identification of nontoxic NAIs. These findings have important implications for the development of all anti-RNA virus NAIs.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.00492-17

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