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Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies

Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B. Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral drugs. The role of the rtI233V mutation and adefo...

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Autores principales: Ismail, Ashrafali Mohamed, Sharma, Om Prakash, Kumar, Muthuvel Suresh, Kannangai, Rajesh, Abraham, Priya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569598/
https://www.ncbi.nlm.nih.gov/pubmed/23423477
http://dx.doi.org/10.6026/97320630009121
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author Ismail, Ashrafali Mohamed
Sharma, Om Prakash
Kumar, Muthuvel Suresh
Kannangai, Rajesh
Abraham, Priya
author_facet Ismail, Ashrafali Mohamed
Sharma, Om Prakash
Kumar, Muthuvel Suresh
Kannangai, Rajesh
Abraham, Priya
author_sort Ismail, Ashrafali Mohamed
collection PubMed
description Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B. Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral drugs. The role of the rtI233V mutation and adefovir resistance remains contradictory. In this study, it was attempted to evaluate the impact of putative rtI233V substitution on adefovir action by homology modeling and docking studies. The HBVrt nucleotide sequence containing rtI233V mutation was obtained from the treatment-naive chronic hepatitis B subject. The three dimensional model of HBV polymerase/rt was constructed using the HIV-1rt template (PDB code: 1RTD A) and the model was evaluated by the Ramachandran plot. Autodock was employed to dock the HBV polymerase/rt and adefovir. The modelled structure showed the amino acid rtI233 to be located away from the drug interactory site. The substitution of isoleucine to valine did not appear to affect the catalytic sites of the protein. In addition, it does not alter the conformation of bent structure formed by residues 235 to 240 that stabilizes the binding of dNTPs. Therefore, it was predicted that rtI233V substitution may not independently affect the antiviral action of adefovir and incoming dNTP binding.
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spelling pubmed-35695982013-02-19 Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies Ismail, Ashrafali Mohamed Sharma, Om Prakash Kumar, Muthuvel Suresh Kannangai, Rajesh Abraham, Priya Bioinformation Hypothesis Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B. Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral drugs. The role of the rtI233V mutation and adefovir resistance remains contradictory. In this study, it was attempted to evaluate the impact of putative rtI233V substitution on adefovir action by homology modeling and docking studies. The HBVrt nucleotide sequence containing rtI233V mutation was obtained from the treatment-naive chronic hepatitis B subject. The three dimensional model of HBV polymerase/rt was constructed using the HIV-1rt template (PDB code: 1RTD A) and the model was evaluated by the Ramachandran plot. Autodock was employed to dock the HBV polymerase/rt and adefovir. The modelled structure showed the amino acid rtI233 to be located away from the drug interactory site. The substitution of isoleucine to valine did not appear to affect the catalytic sites of the protein. In addition, it does not alter the conformation of bent structure formed by residues 235 to 240 that stabilizes the binding of dNTPs. Therefore, it was predicted that rtI233V substitution may not independently affect the antiviral action of adefovir and incoming dNTP binding. Biomedical Informatics 2013-02-06 /pmc/articles/PMC3569598/ /pubmed/23423477 http://dx.doi.org/10.6026/97320630009121 Text en © 2013 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
spellingShingle Hypothesis
Ismail, Ashrafali Mohamed
Sharma, Om Prakash
Kumar, Muthuvel Suresh
Kannangai, Rajesh
Abraham, Priya
Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title_full Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title_fullStr Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title_full_unstemmed Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title_short Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
title_sort impact of rti233v mutation in hepatitis b virus polymerase protein and adefovir efficacy: homology modeling and molecular docking studies
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569598/
https://www.ncbi.nlm.nih.gov/pubmed/23423477
http://dx.doi.org/10.6026/97320630009121
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