Hepatitis E virus (HEV): Strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site

Virus Genes ◽  
1992 ◽  
Vol 6 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Kirk E. Fry ◽  
Albert W. Tam ◽  
Matthew M. Smith ◽  
Jungsuh P. Kim ◽  
Ka-Cheung Luk ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Binding Site ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Gene Region ◽  
Strain Variation ◽  
Rna Dependent Rna Polymerase ◽  
Gtp Binding ◽  
Consensus Motifs

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 Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Nidhi Kaushik ◽  
Chandru Subramani ◽  
Saumya Anang ◽  
Rajagopalan Muthumohan ◽  
Shalimar ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Hepatitis E Virus ◽  
Zinc Supplementation ◽  
Hepatitis E ◽  
Viral Rna ◽  
Health Concern ◽  
Healthy Individuals ◽  
Genomic Rna ◽  
Rna Dependent Rna Polymerase ◽  
Zinc Salts

ABSTRACT Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. IMPORTANCE Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.

scholarly journals Human linear B-cell epitopes encoded by the hepatitis E virus include determinants in the RNA-dependent RNA polymerase.

1992 ◽  
Vol 89 (9) ◽  
pp. 3855-3858 ◽  
Author(s):  
M. Kaur ◽  
K. C. Hyams ◽  
M. A. Purdy ◽  
K. Krawczynski ◽  
W. M. Ching ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
B Cell ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Rna Dependent Rna Polymerase ◽  
B Cell Epitopes ◽  
Linear B

scholarly journals Hepatitis E virus RNA-dependent RNA polymerase: RNA template specificities, recruitment and synthesis

2016 ◽  
Vol 97 (9) ◽  
pp. 2231-2242 ◽  
Author(s):  
Shakuntala Mahilkar ◽  
Mandar S. Paingankar ◽  
Kavita S. Lole
Keyword(s):  
Rna Polymerase ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Rna Dependent Rna Polymerase ◽  
Virus Rna

scholarly journals RNA-dependent RNA Polymerase Assay for Hepatitis E Virus

BIO-PROTOCOL ◽  
2017 ◽  
Vol 7 (7) ◽  
Author(s):  
Vidya Nair ◽  
Saumya Anang ◽  
Akriti Srivastava ◽  
Milan Surjit
Keyword(s):  
Rna Polymerase ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Rna Dependent Rna Polymerase

scholarly journals Mechanism of SARS-CoV-2 polymerase stalling by remdesivir

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Goran Kokic ◽  
Hauke S. Hillen ◽  
Dimitry Tegunov ◽  
Christian Dienemann ◽  
Florian Seitz ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Rna Polymerase ◽  
Binding Site ◽  
Molecular Mechanism ◽  
Active Center ◽  
Rna Synthesis ◽  
Active Form ◽  
Nucleoside Triphosphate ◽  
Rna Dependent Rna Polymerase ◽  
Cryo Electron Microscopy

AbstractRemdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.

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