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Basic Characteristics of Mutations
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Mutation Site
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M50I |
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Mutation Site Sentence
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The alignment also showed 17 NOPs within a South African cohort-derived Subtype C consensus sequence, namely D25E, V31I, M50I, V72I, F100Y, L101I, T112V, T124A, T125A,K136Q, I151V, V201I, T218I, V234I, R269K, D278A, S283G (Supplementary Figure S2). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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IN |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
|
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
|
- |
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Treatment
|
INSTIs |
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Location
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South Africa;Cameroon |
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Literature Information
|
|
PMID
|
32858802
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Title
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Structural Comparison of Diverse HIV-1 Subtypes using Molecular Modelling and Docking Analyses of Integrase Inhibitors
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Author
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Isaacs D,Mikasi SG,Obasa AE,Ikomey GM,Shityakov S,Cloete R,Jacobs GB
|
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Journal
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Viruses
|
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Journal Info
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2020 Aug 26;12(9):936
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Abstract
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The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-naive populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.
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Sequence Data
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-
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