Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient and<i>in silico</i>interaction analysis by molecular docking with Ribavirin

Cancela, Florencia; Rendón-Marín, Santiago; Quintero-Gil, Carolina; Houston, Douglas R.; Gumbis, Gediminas; Panzera, Yanina; Pérez, Ruben; Arbiza, Juan

doi:10.1080/07391102.2021.2011416

Cited by 4 publications

(2 citation statements)

References 129 publications

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“…Ribavirin showed brief interaction with two active sites of RdRp of IBDV in the current study ( Figure 6 ) which is in agreement with previous studies where ribavirin was observed to possess a weak inhibitory activity on RdRp of many RNA viruses viz. HCV, Hepatitis E virus, bovine viral diarrhea virus, vesicular stomatitis virus, influenza virus, reovirus, and HIV in vitro or in silico ( 23 , 24 , 63 ).…”

Section: Discussionmentioning

confidence: 99%

Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool

Akram,

Gul,

Parveez Zia

et al. 2023

Front. Vet. Sci.

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IntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent.MethodsThe cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored.Results and DiscussionRibavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme’s active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus.

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Section: Discussionmentioning

confidence: 99%

Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool

Akram,

Gul,

Parveez Zia

et al. 2023

Front. Vet. Sci.

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“…Some previous studies have involved the use of software such as Pymol, Pyrex, and Protein Plus to perform docking analysis and predict molecular interactions. [6][7][8] However, no studies have specifically investigated the potential of Rosmarinic Acid as an inhibitor of Hepatitis E by interacting with the Tyrosine FYN protein. Therefore, this research fills the existing knowledge gap by presenting a comprehensive computational analysis of the interaction between Rosmarinic Acid and the target protein of Hepatitis E, which can provide a better understanding of the potential mechanism of action of this compound and serve as a basis for the development of new, more effective therapies.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis E Inhibited by Rosmarinic Acid Extract from Clove Plant (Syzygium Aromaricum) through Computational Analysis

Sunadi,

Al Aziz,

Fitri

et al. 2023

Pharmacogn J.

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This study aims to evaluate the potential of Rosmarinic Acid as an inhibitor against Hepatitis E by interacting with the active site of the Tyrosine FYN protein. Computational approaches were employed to predict the molecular interactions between Rosmarinic Acid and Tyrosine FYN. The research methodology involved the use of software such as Pymol, Pyrex, Protein Plus, and the Lepinski Rule. Docking analysis was conducted using Pymol to obtain information about the binding energy between Rosmarinic Acid and Tyrosine FYN. The results of the analysis showed that Rosmarinic Acid exhibited a Binding Affinity of -8.3, -8, and -7.9, indicating a strong affinity towards the target protein. Additionally, Root Mean Square Deviation (RMSD) values of 0, 15.905, and 17.014 were used to assess the stability of the formed protein-ligand complex. Analysis using Protein Plus revealed interactions between Rosmarinic Acid and Tyrosine FYN. Furthermore, analysis using the Lepinski Rule to examine the physicochemical properties of Rosmarinic Acid indicated that the molecule had a mass of 360, 5 hydrogen bond donors, 8 hydrogen bond acceptors, a log P value of 1.76, and a molar reactivity of 89.8. These findings highlight the potential of Rosmarinic Acid as an inhibitor of Hepatitis E through its interaction with the Tyrosine FYN protein, providing a basis for the development of potential new therapies in the treatment of this disease.

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Free-Docking and Template-Based Docking: Physics Versus Knowledge-Based Docking

Krupa,

Krupa

2024

Protein-Protein Docking

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Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient andin silicointeraction analysis by molecular docking with Ribavirin

Cited by 4 publications

References 129 publications

Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool

Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool

Hepatitis E Inhibited by Rosmarinic Acid Extract from Clove Plant (Syzygium Aromaricum) through Computational Analysis

Free-Docking and Template-Based Docking: Physics Versus Knowledge-Based Docking

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