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Volume 19   Issue 1   Year 2024
Using a Drug Repurposing Strategy to Virtually Screen Potential HIV-1 Entry Inhibitors That Block the NHR Domain of the Viral Envelope Protein gp41

Andrianov A.M.1, Laykov Y.V.2, Tuzikov A.V.2

1Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
2United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, Belarus

Abstract. Using a drug repurposing strategy, virtual screening of potential inhibitors of the NHR domain of the HIV-1 gp41 protein, a conserved region critical for the virus-cell membrane fusion and viral infectivity, was carried out. The used computational approach included: (1) molecular docking of this functionally significant region of the HIV-1 envelope with compounds from a library of bioactive molecules containing clinically approved drugs, experimental drugs, and investigational drug candidates; (2) assessing the binding affinity of these compounds to the therapeutic target; (3) molecular dynamics simulations of ligand/NHR-gp41 complexes; (4) calculations of the binding free energy followed by the analysis of molecular dynamics trajectories and selection of compounds promising to test for anti-HIV-1 activity. As a result, six compounds that exhibited the high binding affinity to the NHR domain of the HIV-1 gp41 protein and showed acceptable pharmacological properties were identified. The predicted compounds are assumed to form a promising basis for the development of new, effective and safe broad-spectrum antiviral agents able to inhibit the HIV-1 entry into the host cell.


Key words: HIV-1, protein gp41, domain NHR, virtual screening, molecular docking, molecular dynamics, anti-HIV drugs.

Table of Contents Original Article
Math. Biol. Bioinf.
doi: 10.17537/2024.19.77
published in Russian

Abstract (rus.)
Abstract (eng.)
Full text (rus., pdf)


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