scholarly journals Mutations in the GDD Motif of Rubella Virus Putative RNA-Dependent RNA Polymerase Affect Virus Replication

Virology ◽  
2001 ◽  
Vol 285 (2) ◽  
pp. 322-331 ◽  
Author(s):  
Xiaojie Wang ◽  
Shirley Gillam
Keyword(s):  
Rna Polymerase ◽  
Virus Replication ◽  
Rubella Virus ◽  
Rna Dependent Rna Polymerase ◽  
Gdd Motif

scholarly journals Ubiquitination Is Essential for Avibirnavirus Replication by Supporting VP1 Polymerase Activity

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
Huansheng Wu ◽  
Liuyuan Shi ◽  
Yina Zhang ◽  
Xiran Peng ◽  
Tuyuan Zheng ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Virus Replication ◽  
Mutation Screening ◽  
Polymerase Activity ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Rna Dependent Rna Polymerase ◽  
Ubiquitin Chain ◽  
Vp1 Protein ◽  
C Terminus

ABSTRACTUbiquitination is critical for several cellular physical processes. However, ubiquitin modification in virus replication is poorly understood. Therefore, the present study aimed to determine the presence and effect of ubiquitination on polymerase activity of viral protein 1 (VP1) of avibirnavirus. We report that the replication of avibirnavirus is regulated by ubiquitination of its VP1 protein, the RNA-dependent RNA polymerase of infectious bursal disease virus (IBDV).In vivodetection revealed the ubiquitination of VP1 protein in IBDV-infected target organs and different cells but not in purified IBDV particles. Further analysis of ubiquitination confirms that VP1 is modified by K63-linked ubiquitin chain. Point mutation screening showed that the ubiquitination site of VP1 was at the K751 residue in the C terminus. The K751 ubiquitination is independent of VP1’s interaction with VP3 and eukaryotic initiation factor 4A II. Polymerase activity assays indicated that the K751 ubiquitination at the C terminus of VP1 enhanced its polymerase activity. The K751-to-R mutation of VP1 protein did not block the rescue of IBDV but decreased the replication ability of IBDV. Our data demonstrate that the ubiquitination of VP1 is crucial to regulate its polymerase activity and IBDV replication.IMPORTANCEAvibirnavirus protein VP1, the RNA-dependent RNA polymerase, is responsible for IBDV genome replication, gene expression, and assembly. However, little is known about its chemical modification relating to its polymerase activity. In this study, we revealed the molecular mechanism of ubiquitin modification of VP1 via a K63-linked ubiquitin chain during infection. Lysine (K) residue 751 at the C terminus of VP1 is the target site for ubiquitin, and its ubiquitination is independent of VP1’s interaction with VP3 and eukaryotic initiation factor 4A II. The K751 ubiquitination promotes the polymerase activity of VP1 and unubiquitinated VP1 mutant IBDV significantly impairs virus replication. We conclude that VP1 is the ubiquitin-modified protein and reveal the mechanism by which VP1 promotes avibirnavirus replication.

In-vitro inhibition of spring viremia of carp virus replication by RNA interference targeting the RNA-dependent RNA polymerase gene

2019 ◽  
Vol 263 ◽  
pp. 14-19 ◽  
Author(s):  
Alamira Marzouk Fouad ◽  
Hatem Soliman ◽  
Ebtsam S.H. Abdallah ◽  
Sherif Ibrahim ◽  
Mansour El-Matbouli ◽  
...  
Keyword(s):  
Rna Interference ◽  
Rna Polymerase ◽  
Virus Replication ◽  
Polymerase Gene ◽  
Rna Dependent Rna Polymerase ◽  
In Vitro Inhibition ◽  
Rna Polymerase Gene

scholarly journals Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

2017 ◽  
Vol 32 (1) ◽  
pp. 1091-1101 ◽  
Author(s):  
Sveva Pelliccia ◽  
Yu-Hsuan Wu ◽  
Antonio Coluccia ◽  
Giuseppe La Regina ◽  
Chin-Kai Tseng ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Polymerase ◽  
Virus Replication ◽  
Rna Dependent Rna Polymerase

3′,5′di-O-Trityluridine Inhibits Flavivirus (Dengue and Yellow Fever Virus) Replication and Targets the Viral RNA Dependent RNA Polymerase

2011 ◽  
Vol 90 (2) ◽  
pp. A55
Author(s):  
Tine De Burghgraeve ◽  
Suzanne J.F. Kaptein ◽  
Kai Dallmeier ◽  
Barbara Selisko ◽  
Michael Jacobs ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Viral Rna ◽  
Rna Dependent Rna Polymerase

Phyto-compounds from a rather poisonous plant, Strychnos nux-vomica, show high potency against SARS-CoV-2 RNA-dependent RNA polymerase

2021 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Subarna Pokhrel ◽  
Anurag Varshney
Keyword(s):  
Rna Polymerase ◽  
Virus Replication ◽  
Dissociation Constants ◽  
Binding Free Energy ◽  
Binding Affinities ◽  
Free Energies ◽  
Poisonous Plant ◽  
Rna Dependent Rna Polymerase ◽  
Signature Sequence

Background: Strategy to inhibit the virus replication is an attractive means in combating SARS-CoV-2 infection. Objective: We studied phyto-compounds from Strychnos nux-vomica (a poisonous plant) against SARS-CoV-2 RNA-dependent RNA polymerase by computational methods. Method: Molecular docking, molecular dynamics (MD) simulation and energetics calculations were employed to elucidate the role of the phyto-compounds. Results: Ergotamine with a binding free energy of -14.39 kcal/mol showed a promising capability in terms of both the binding affinity and interacting to conserved motifs, especially the SDD signature sequence. The calculated dissociation constants for ATP, ergotamine, isosungucine and sungucine were 12 µM, 0.072 nM, 0.011 nM and 0.152 nM, respectively. The exhibited kd by these phyto-compounds reflected a tens of thousands fold potency as compared to ATP. The binding free energies of sungucine and isosungucine were much lower (-13.93 and -15.55 kcal/mol, respectively) compared to that of ATP (-6.98 kcal/mol). Conclusion: Sharing the same binding location as that of ATP and having high binding affinities, Ergotamine, Isosungucine, Sungucine and Strychnine N-oxide could be effective in controlling the SARS-CoV-2 virus replication by blocking the ATP and inhibiting the enzyme function.

scholarly journals Norovirus Proteinase-Polymerase and Polymerase Are Both Active Forms of RNA-Dependent RNA Polymerase

2005 ◽  
Vol 79 (4) ◽  
pp. 2393-2403 ◽  
Author(s):  
Gaël Belliot ◽  
Stanislav V. Sosnovtsev ◽  
Kyeong-Ok Chang ◽  
Vijay Babu ◽  
Uzo Uche ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Virus Replication ◽  
Acute Gastroenteritis ◽  
Cleavage Site ◽  
Active Form ◽  
Feline Calicivirus ◽  
Bifunctional Enzyme ◽  
Rdrp Activity ◽  
Rna Dependent Rna Polymerase

ABSTRACT In vitro mapping studies of the MD145 norovirus (Caliciviridae) ORF1 polyprotein identified two stable cleavage products containing the viral RNA-dependent RNA polymerase (RdRp) domains: ProPol (a precursor comprised of both the proteinase and polymerase) and Pol (the mature polymerase). The goal of this study was to identify the active form (or forms) of the norovirus polymerase. The recombinant ProPol (expressed as Pro−Pol with an inactivated proteinase domain to prevent autocleavage) and recombinant Pol were purified after synthesis in bacteria and shown to be active RdRp enzymes. In addition, the mutant His-E1189A-ProPol protein (with active proteinase but with the natural ProPol cleavage site blocked) was active as an RdRp, confirming that the norovirus ProPol precursor could possess two enzymatic activities simultaneously. The effects of several UTP analogs on the RdRp activity of the norovirus and feline calicivirus Pro−Pol enzymes were compared and found to be similar. Our data suggest that the norovirus ProPol is a bifunctional enzyme during virus replication. The availability of this recombinant ProPol enzyme might prove useful in the development of antiviral drugs for control of the noroviruses associated with acute gastroenteritis.

Sign in / Sign up

Export Citation Format

Share Document