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Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors
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SYSNO ASEP 0571224 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors Author(s) Pávová, Marcela (UOCHB-X)
Reyes Gutierrez, Paul Eduardo (UOCHB-X) RID, ORCID
Kozák, Jaroslav (UOCHB-X) RID, ORCID
Dobiaš, Juraj (UOCHB-X) ORCID
Yurenko, Yevgen (UOCHB-X)
Lepšík, Martin (UOCHB-X) RID, ORCID
Teplý, Filip (UOCHB-X) RID, ORCID
Weber, Jan (UOCHB-X) RID, ORCIDArticle number 6096 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 13, April (2023)Number of pages 13 s. Language eng - English Country US - United States Keywords long terminal repeat ; promoter ; binding OECD category Virology R&D Projects LX22NPO5103 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure e-INFRA CZ - 90140 - CESNET, zájmové sdružení právnických osob Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 000984454500085 EID SCOPUS 85152381657 DOI 10.1038/s41598-023-33263-3 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1038/s41598-023-33263-3
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