Repurposing integrase inhibitors against human T-lymphotropic virus type-1: a computational approach.

in Journal of biomolecular structure & dynamics by Prashasti Sinha, Anil Kumar Yadav

TLDR

  • Researchers identified three integrase antivirals, Cabotegravir, Raltegravir, and Elvitegravir, that may be effective against HTLV-1 infection, which causes ATL.
  • These medications showed promising results in molecular docking modeling and dynamics simulation, but require further clinical testing to confirm their efficacy.
  • The study demonstrates the potential of drug repurposing and molecular modeling in identifying new therapies for ATL and other diseases.

Abstract

Adult T-cell Lymphoma (ATL) is caused by the delta retrovirus family member known as Human T-cell Leukaemia Type I (HTLV-1). Due to the unavailability of any cure, the study gained motivation to identify some repurposed drugs against the virus. A quick and accurate method of screening licensed medications for finding a treatment for HTLV-1 is by cheminformatics drug repurposing in order to analyze a dataset of FDA approved integrase antivirals against HTLV-1 infection. To determine how the antiviral medications interacted with the important residues in the HTLV-1 integrase active regions, molecular docking modeling was used. The steady behavior of the ligands inside the active region was then confirmed by molecular dynamics for the probable receptor-drug complexes. Cabotegravir, Raltegravir and Elvitegravir had the best docking scores with the target, indicating that they can tightly bind to the HTLV-1 integrase. Moreover, MD simulation revealed that the Cabotegravir-HTLV-1, Raltegravir-HTLV-1 and Elvitegravir-HTLV-1 interactions were stable. It is obvious that more testing of these medicines in both clinical trials and experimental tests is necessary to demonstrate their efficacy against HTLV-1 infection.

Overview

  • The study aimed to identify repurposed drugs against Human T-cell Leukemia Type I (HTLV-1), a virus causing Adult T-cell Lymphoma (ATL).
  • Cheminformatics drug repurposing and molecular docking modeling were used to analyze FDA-approved integrase antivirals against HTLV-1 infection.
  • The primary objective was to identify licensed medications that can inhibit HTLV-1 integrase, as a potential treatment for ATL.

Comparative Analysis & Findings

  • Molecular docking modeling revealed that Cabotegravir, Raltegravir, and Elvitegravir had the best docking scores with the target HTLV-1 integrase, indicating tight binding.
  • Molecular dynamics simulation confirmed the stability of the ligand-receptor complexes, Cabotegravir-HTLV-1, Raltegravir-HTLV-1, and Elvitegravir-HTLV-1.
  • These findings suggest that these medications may be effective against HTLV-1 infection, but further testing is necessary to confirm their efficacy.

Implications and Future Directions

  • Future studies should investigate the clinical efficacy of Cabotegravir, Raltegravir, and Elvitegravir against HTLV-1 infection in clinical trials and experimental tests.
  • The study highlights the potential of cheminformatics drug repurposing and molecular modeling in identifying new therapies for ATL and other diseases.
  • Additional research is needed to understand the mechanisms of action of these medications against HTLV-1 integrase and to identify potential side effects or drug interactions.
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