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

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.

Communicated by Ramaswamy H. Sarma

Keywords:

• HTLV-1
• integrase
• molecular docking
• MD simulation
• raltegravir

Acknowledgment

Author, Prashasti Sinha is very thankful to the University Grant Commission (UGC), New Delhi, India, for the financial support for doctoral research work. Authors would like to acknowledge IIT Delhi, India for allowing the access of SCFBio web server.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.