Kasetsart University; National Science & Technology Development Agency - Thailand; Kasetsart University; Kasetsart University; National Institutes of Natural Sciences (NINS) - Japan; The Exploratory Research Center on Life & Living Systems (ExCELLS); National Institutes of Natural Sciences (NINS) - Japan; Institute for Molecular Science (IMS)
Type
Article
Source Title
MOLECULES
Year
2022
Volume
27
Issue
1
Page
-
Open Access
Green Published, gold
Publisher
MDPI
DOI
10.3390/molecules27010285
Format
PDF
Abstract
The human immunodeficiency virus type-1 Reverse Transcriptase (HIV-1 RT) plays a pivotal role in essential viral replication and is the main target for antiviral therapy. The anti-HIV-1 RT drugs address resistance-associated mutations. This research focused on isolating the potential specific DNA aptamers against K103N/Y181C double mutant HIV-1 RT. Five DNA aptamers showed low IC50 values against both the KY-mutant HIV-1 RT and wildtype (WT) HIV-1 RT. The kinetic binding affinity forms surface plasmon resonance of both KY-mutant and WT HIV-1 RTs in the range of 0.06-2 mu M and 0.15-2 mu M, respectively. Among these aptamers, the KY44 aptamer was chosen to study the interaction of HIV-1 RTs-DNA aptamer complex by NMR experiments. The NMR results indicate that the aptamer could interact with both WT and KY-mutant HIV-1 RT at the NNRTI drug binding pocket by inducing a chemical shift at methionine residues. Furthermore, KY44 could inhibit pseudo-HIV particle infection in HEK293 cells with nearly 80% inhibition and showed low cytotoxicity on HEK293 cells. These together indicated that the KY44 aptamer could be a potential inhibitor of both WT and KY-mutant HIV-RT.
