scholarly journals Potent Non-Nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase Complex

2008 ◽  
Vol 51 (13) ◽  
pp. 3731-3741 ◽  
Author(s):  
Aiming Sun ◽  
Jeong-Joong Yoon ◽  
Yan Yin ◽  
Andrew Prussia ◽  
Yutao Yang ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Measles Virus ◽  
Rna Dependent Rna Polymerase ◽  
Polymerase Complex ◽  
Virus Rna ◽  
Nucleoside Inhibitors

scholarly journals Non-nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase: Synthesis, Structure–Activity Relationships, and Pharmacokinetics

2012 ◽  
Vol 55 (9) ◽  
pp. 4220-4230 ◽  
Author(s):  
J. Maina Ndungu ◽  
Stefanie A. Krumm ◽  
Dan Yan ◽  
Richard F. Arrendale ◽  
G. Prabhakar Reddy ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Measles Virus ◽  
Rna Dependent Rna Polymerase ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Virus Rna ◽  
Nucleoside Inhibitors

An Amino-Proximal Domain of the L Protein Binds to the P Protein in the Measles Virus RNA Polymerase Complex

Virology ◽  
1994 ◽  
Vol 205 (2) ◽  
pp. 540-545 ◽  
Author(s):  
Sandra M. Horikami ◽  
Sherin Smallwood ◽  
Bettina Bankamp ◽  
Sue A. Moyer
Keyword(s):  
Rna Polymerase ◽  
Measles Virus ◽  
Polymerase Complex ◽  
L Protein ◽  
P Protein ◽  
Virus Rna

Biochemical Characterization of Respiratory Syncytial Virus RNA-Dependent RNA Polymerase Complex

2020 ◽  
Vol 6 (10) ◽  
pp. 2800-2811
Author(s):  
Anand Balakrishnan ◽  
Edmund Price ◽  
Catherine Luu ◽  
Jacob Shaul ◽  
Charles Wartchow ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rna Polymerase ◽  
Biochemical Characterization ◽  
Rna Dependent Rna Polymerase ◽  
Polymerase Complex ◽  
Virus Rna ◽  
Syncytial Virus

scholarly journals Nonnucleoside Inhibitor of Measles Virus RNA-Dependent RNA Polymerase Complex Activity

2007 ◽  
Vol 51 (7) ◽  
pp. 2293-2303 ◽  
Author(s):  
Laura K. White ◽  
Jeong-Joong Yoon ◽  
Jin K. Lee ◽  
Aiming Sun ◽  
Yuhong Du ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
High Throughput Screening ◽  
Measles Virus ◽  
Specific Inhibitor ◽  
Cross Resistance ◽  
Complex Activity ◽  
Rna Dependent Rna Polymerase ◽  
Developmental Potential ◽  
Polymerase Complex ◽  
Fusion Inhibitors

ABSTRACT Paramyxoviruses comprise several major human pathogens. Although a live-attenuated vaccine protects against measles virus (MV), a member of the paramyxovirus family, the virus remains a principal cause of worldwide mortality and accounts for approximately 21 million cases and 300,000 to 400,000 deaths annually. The development of novel antivirals that allow improved case management of severe measles and silence viral outbreaks is thus highly desirable. We have previously described the development of novel MV fusion inhibitors. The potential for preexisting or emerging resistance in the field constitutes the rationale for the identification of additional MV inhibitors with a diverse target spectrum. Here, we report the development and implementation of a cell-based assay for high-throughput screening of MV antivirals, which has yielded several hit candidates. Following confirmation by secondary assays and chemical synthesis, the most potent hit was found to act as a target-specific inhibitor of MV replication with desirable drug-like properties. The compound proved highly active against multiple primary isolates of diverse MV genotypes currently circulating worldwide, showing active concentrations of 35 to 145 nM. Significantly, it does not interfere with viral entry and lacks cross-resistance with the MV fusion inhibitor class. Mechanistic characterization on a subinfection level revealed that the compound represents a first-in-class nonnucleoside inhibitor of MV RNA-dependent RNA polymerase complex activity. Singly or in combination with the fusion inhibitors, this novel compound class has high developmental potential as a potent therapeutic against MV and will likely further the mechanistic characterization of the viral polymerase complex.

New Non-nucleoside Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

2004 ◽  
Vol 69 (7) ◽  
pp. 782-788 ◽  
Author(s):  
A. V. Ivanov ◽  
M. V. Kozlov ◽  
A. O. Kuzyakin ◽  
D. A. Kostyuk ◽  
V. L. Tunitskaya ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Polymerase ◽  
Hepatitis C Virus Rna ◽  
Rna Dependent Rna Polymerase ◽  
Virus Rna ◽  
Nucleoside Inhibitors

scholarly journals Hepatitis E Virus RNA‐Dependent RNA Polymerase is Involved in RNA Replication and Infectious Particle Production

Hepatology ◽  
2021 ◽  
Author(s):  
Noémie Oechslin ◽  
Nathalie Da Silva ◽  
Dagmara Szkolnicka ◽  
François‐Xavier Cantrelle ◽  
Xavier Hanoulle ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Hepatitis E Virus ◽  
Particle Production ◽  
Rna Replication ◽  
Hepatitis E ◽  
Rna Dependent Rna Polymerase ◽  
Infectious Particle ◽  
Virus Rna

scholarly journals Analysis of Ribonucleotide 5′-Triphosphate Analogs as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase by Using Nonradioactive Polymerase Assays

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Gaofei Lu ◽  
Gregory R. Bluemling ◽  
Paul Collop ◽  
Michael Hager ◽  
Damien Kuiper ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Rna Dependent Rna Polymerase ◽  
Antiviral Compounds ◽  
Double Stranded Dna ◽  
Virus Rna ◽  
Potential Inhibitors

ABSTRACT Zika virus (ZIKV) is an emerging human pathogen that is spreading rapidly through the Americas and has been linked to the development of microcephaly and to a dramatically increased number of Guillain-Barré syndrome cases. Currently, no vaccine or therapeutic options for the prevention or treatment of ZIKV infections exist. In the study described in this report, we expressed, purified, and characterized full-length nonstructural protein 5 (NS5) and the NS5 polymerase domain (NS5pol) of ZIKV RNA-dependent RNA polymerase. Using purified NS5, we developed an in vitro nonradioactive primer extension assay employing a fluorescently labeled primer-template pair. Both purified NS5 and NS5pol can carry out in vitro RNA-dependent RNA synthesis in this assay. Our results show that Mn2+ is required for enzymatic activity, while Mg2+ is not. We found that ZIKV NS5 can utilize single-stranded DNA but not double-stranded DNA as a template or a primer to synthesize RNA. The assay was used to compare the efficiency of incorporation of analog 5′-triphosphates by the ZIKV polymerase and to calculate their discrimination versus that of natural ribonucleotide triphosphates (rNTPs). The 50% inhibitory concentrations for analog rNTPs were determined in an alternative nonradioactive coupled-enzyme assay. We determined that, in general, 2′-C-methyl- and 2′-C-ethynyl-substituted analog 5′-triphosphates were efficiently incorporated by the ZIKV polymerase and were also efficient chain terminators. Derivatives of these molecules may serve as potential antiviral compounds to be developed to combat ZIKV infection. This report provides the first characterization of ZIKV polymerase and demonstrates the utility of in vitro polymerase assays in the identification of potential ZIKV inhibitors.

Sign in / Sign up

Export Citation Format

Share Document