Exploring the drug resistance mechanism of active site, non-active site mutations and their cooperative effects in CRF01_AE HIV-1 protease: molecular dynamics simulations and free energy calculations.
PMID: 30051758
2019
Journal of biomolecular structure & dynamics
Abstract: In this work, we have investigated the mechanism of resistance against indinavir (IDV) due to therapy selected active site mutation V82F, non-active site mutations PF82V and their cooperative effects PV82F in subtype AE-protease using molecular dynamics simulations and binding free energy calculations.
Abstract: Large positional deviation of IDV was observed in V82F complex.
Abstract: The simulations suggested all the three complexes lead to decrease in binding affinity of IDV, whereas the PF82V complex resulted in an enhanced binding affinity compared to V82F and PV82F complexes.
High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO.
PMID: 30891603
2019
The Journal of antimicrobial chemotherapy
Result: DRMs to PIs corresponded mainly to natural polymorphism in the P gene while only the major DRMs V82A/F (n = 3; 20%) and L33F (n = 1, 6.7%) could be found.
Discussion: However, in the presence of G48V flap mutation, mutations of residue 82 to larger side chains like
Discussion: The side chains of mutations vary in size from the smaller V82A to bulkier V82F in addition to V82S, V82T, V82L, and V82I that are in between.
Discussion: With P3 Arg bound at the preferred wild-type flap-binding site, mutations at 82 with large side chains like V82F, V82I, or V82L hinder the binding of PR inhibitors, thereby altering PR susceptibility to PIs while retaining binding to substrates.
Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study.
Method: Participants with a history of genotypic/phenotypic drug resistance to protease inhibitors (PIs) or with HIV-1 genotypic drug resistance to PIs at baseline (including D30N, M46I/L, I47V/A, G48V, I50L, I54M/L, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, or L90M) were excluded, despite any reported effects of PI resistance or resistance
HIV-1 transmission networks across Cyprus (2010-2012).
Result: The second study subject, also a Romanian citizen living in Cyprus, was also infected with a sub-subtype F1strain dual-class RT and PI resistant strain carrying D67N, K70R, M184V, T215F, Y181C, M46L, I54V and V82F mutations associated with drug resistance.
[Genetic analysis of the mutations in HIV-1 infected population in Ecuador].
PMID: 29652972
2018
Revista chilena de infectologia
Abstract: Results The most frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M in children.
Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).
Method: Primary PI-R substitutions assessed were D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54L/M, Q58E, T74P, L76V, V82A/F/L/S/T, I84V, N88S, and L90M in PR.
Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.
PMID: 28328546
2017
Journal of acquired immune deficiency syndromes (1999)
Result: The most common PI mutations were V82A/T/F/S/I; V32I mutation was present in 3 cases, and has been associated with high level of resistance in combination with other PI mutations.
Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.
Result: The major virus (referred to as FS5929R1) had two major DRV resistance mutations (I47V and I50V), four minor mutations (V11I, V32I, L33F, and L89V), and V82F.
Table: V82F
Discussion: Therefore, the curling conformation would also shield these residues, resulting in the inhibition of DRV binding to monomeric PR; in contrast, the presence of four mutations (V32I, L33F, I54V, and V82F) in FS5929R1 PR might directly impair the DRV binding to monomeric PR.
Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics.
HIV mutation literature information.
PMID: 
2019
Journal of biomolecular structure & dynamics
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