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 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 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 Efficient Interaction between Arenavirus Nucleoprotein (NP) and RNA-Dependent RNA Polymerase (L) Is Mediated by the Virus Nucleocapsid (NP-RNA) Template

2015 ◽  
Vol 89 (10) ◽  
pp. 5734-5738 ◽  
Author(s):  
Masaharu Iwasaki ◽  
Nhi Ngo ◽  
Beatrice Cubitt ◽  
Juan C. de la Torre
Keyword(s):  
Rna Polymerase ◽  
Gene Transcription ◽  
Viral Genome ◽  
Rna Replication ◽  
Rna Dependent Rna Polymerase ◽  
Rna Sequences ◽  
L Protein ◽  
Virus Rna

In this study, we document that efficient interaction between arenavirus nucleoprotein (NP) and RNA-dependent RNA polymerase (L protein), the twotrans-acting viral factors required for both virus RNA replication and gene transcription, requires the presence of virus-specific RNA sequences located within the untranslated 5′ and 3′ termini of the viral genome.

Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

2020 ◽  
Author(s):  
Feroza Begum ◽  
UPASANA RAY
Keyword(s):  
Rna Polymerase ◽  
Particle Production ◽  
Drug Repurposing ◽  
Viral Rna ◽  
Rna Dependent Rna Polymerase ◽  
Domain Specific ◽  
Virus Rna ◽  
Promising Area ◽  
Screening And Identification ◽  
Approved Drugs

<p>The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding. </p>

scholarly journals Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

2020 ◽  
Author(s):  
Feroza Begum ◽  
UPASANA RAY
Keyword(s):  
Rna Polymerase ◽  
Particle Production ◽  
Drug Repurposing ◽  
Viral Rna ◽  
Rna Dependent Rna Polymerase ◽  
Domain Specific ◽  
Virus Rna ◽  
Promising Area ◽  
Screening And Identification ◽  
Approved Drugs

<p>The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding. </p>

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