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Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1

Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient...

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Detalles Bibliográficos
Autores principales: Glumakova, Ksenia, Ivanov, Georgy, Vedernikova, Valeria, Shyrokova, Lena, Lebedev, Timofey, Stomakhin, Andrei, Zenchenko, Anastasia, Oslovsky, Vladimir, Drenichev, Mikhail, Prassolov, Vladimir, Spirin, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610023/
https://www.ncbi.nlm.nih.gov/pubmed/37896149
http://dx.doi.org/10.3390/pharmaceutics15102389
Descripción
Sumario:Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient antivirals. Here the efficiency of HIV-1 inhibition by a set of original 5-substituted uridine nucleosides was studied. We used the replication deficient human immunodeficiency virus (HIV-1)-based lentiviral particles and identified that among the studied compounds, 2′,3′-isopropylidene-5-iodouridine was shown to cause anti-HIV-1 activity. Importantly, no toxic action of this compound against the cells of T-cell origin was found. We determined that this compound is significantly more efficient at suppressing HIV-1 compared to Azidothymidine (AZT) when taken at the high non-toxic concentrations. We did not find any profit when using AZT in combination with 2′,3′-isopropylidene-5-iodouridine. 2′,3′-Isopropylidene-5-iodouridine acts synergistically to repress HIV-1 when combined with the CDK4/6 inhibitor Palbociclib in low non-toxic concentration. No synergistic antiviral action was detected when AZT was combined with Palbociclib. We suggest 2′,3′-isopropylidene-5-iodouridine as a novel perspective non-toxic compound that may be used for HIV-l suppression.