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

0571224 - ÚOCHB 2024 RIV US eng J - Journal Article
Pávová, Marcela - Reyes Gutierrez, Paul Eduardo - Kozák, Jaroslav - Dobiaš, Juraj - Yurenko, Yevgen - Lepšík, Martin - Teplý, Filip - Weber, Jan
Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.
Scientific Reports. Roč. 13, April (2023), č. článku 6096. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Research Infrastructure: e-INFRA CZ - 90140
Institutional support: RVO:61388963
Keywords : long terminal repeat * promoter * binding
OECD category: Virology
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1038/s41598-023-33263-3

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.
Permanent Link: https://hdl.handle.net/11104/0342496