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Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.

ABSTRACT: The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 long terminal repeat promoter region and their stabilization results in the inhibition of HIV-1 replication. Here, we identified helquat-based compounds as a new class of anti-HIV-1 inhibitors that inhibit HIV-1 replication at the stage of reverse transcription and provirus expression. Using Taq polymerase stop and FRET melting assays, we have demonstrated their ability to stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. Moreover, these compounds were not binding to the general G-rich region, but rather to G-quadruplex-forming regions. Finally, docking and molecular dynamics calculations indicate that the structure of the helquat core greatly affects the binding mode to the individual G-quadruplexes. Our findings can provide useful information for the further rational design of inhibitors targeting G-quadruplexes in HIV-1.

SUBMITTER: Pavova M

PROVIDER: S-EPMC10102027 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.

Pávová Marcela M Reyes-Gutiérrez Paul Eduardo PE Kozák Jaroslav J Dobiaš Juraj J Yurenko Yevgen Y Lepšík Martin M Teplý Filip F Weber Jan J

Scientific reports 20230413 1

The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 long terminal repeat promoter region and their stabilization results in the inhibition of HIV-1 replication. Here, we identified helquat-based compounds as a new class of anti-HIV-1 inhibitors that inhibit HIV-1 replication at the stage of reverse transcription and provirus expression. Using Taq po ...[more]

PMID: 37055553

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Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.

Publications

Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.

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