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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Biomedical Informatics
2013
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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. |
format | Online Article Text |
id | pubmed-3569598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Biomedical Informatics |
record_format | MEDLINE/PubMed |
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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