Proposal of pharmacophore model for HIV reverse transcriptase inhibitors: Combined mutational effect analysis, molecular dynamics, molecular docking and pharmacophore modeling study ...
SAGE Journals, 2024
academicJournal
Zugriff:
Objectives: Antiretroviral therapy (ART) efficacy is jeopardized by the emergence of drug resistance mutations in HIV, compromising treatment effectiveness. This study aims to propose novel analogs of Effavirenz (EFV) as potential direct inhibitors of HIV reverse transcriptase, employing computer-aided drug design methodologies. Methods: Three key approaches were applied: a mutational profile study, molecular dynamics simulations, and pharmacophore development. The impact of mutations on the stability, flexibility, function, and affinity of target proteins, especially those associated with NRTI, was assessed. Molecular dynamics analysis identified G190E as a mutation significantly altering protein properties, potentially leading to therapeutic failure. Comparative analysis revealed that among six first-line antiretroviral drugs, EFV exhibited notably low affinity with viral reverse transcriptase, further reduced by the G190E mutation. Subsequently, a search for EFV-similar inhibitors yielded 12 promising ...
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Proposal of pharmacophore model for HIV reverse transcriptase inhibitors: Combined mutational effect analysis, molecular dynamics, molecular docking and pharmacophore modeling study ...
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Autor/in / Beteiligte Person: | Annan, Azzeddine ; Raiss, Noureddine ; Lemrabet, Sanae ; Elomari, Nezha ; Elmir, El Harti ; Filali-Maltouf, Abdelkarim ; Medraoui, Leila ; Oumzil, Hicham |
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Veröffentlichung: | SAGE Journals, 2024 |
Medientyp: | academicJournal |
DOI: | 10.25384/sage.c.7054466.v1 |
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