Cargando…

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...

Descripción completa

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
_version_ 1785128153144885248
author Glumakova, Ksenia
Ivanov, Georgy
Vedernikova, Valeria
Shyrokova, Lena
Lebedev, Timofey
Stomakhin, Andrei
Zenchenko, Anastasia
Oslovsky, Vladimir
Drenichev, Mikhail
Prassolov, Vladimir
Spirin, Pavel
author_facet Glumakova, Ksenia
Ivanov, Georgy
Vedernikova, Valeria
Shyrokova, Lena
Lebedev, Timofey
Stomakhin, Andrei
Zenchenko, Anastasia
Oslovsky, Vladimir
Drenichev, Mikhail
Prassolov, Vladimir
Spirin, Pavel
author_sort Glumakova, Ksenia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10610023
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106100232023-10-28 Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 Glumakova, Ksenia Ivanov, Georgy Vedernikova, Valeria Shyrokova, Lena Lebedev, Timofey Stomakhin, Andrei Zenchenko, Anastasia Oslovsky, Vladimir Drenichev, Mikhail Prassolov, Vladimir Spirin, Pavel Pharmaceutics Article 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. MDPI 2023-09-27 /pmc/articles/PMC10610023/ /pubmed/37896149 http://dx.doi.org/10.3390/pharmaceutics15102389 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Glumakova, Ksenia
Ivanov, Georgy
Vedernikova, Valeria
Shyrokova, Lena
Lebedev, Timofey
Stomakhin, Andrei
Zenchenko, Anastasia
Oslovsky, Vladimir
Drenichev, Mikhail
Prassolov, Vladimir
Spirin, Pavel
Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title_full Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title_fullStr Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title_full_unstemmed Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title_short Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
title_sort nucleoside analog 2′,3′-isopropylidene-5-iodouridine as novel efficient inhibitor of hiv-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610023/
https://www.ncbi.nlm.nih.gov/pubmed/37896149
http://dx.doi.org/10.3390/pharmaceutics15102389
work_keys_str_mv AT glumakovaksenia nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT ivanovgeorgy nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT vedernikovavaleria nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT shyrokovalena nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT lebedevtimofey nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT stomakhinandrei nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT zenchenkoanastasia nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT oslovskyvladimir nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT drenichevmikhail nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT prassolovvladimir nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1
AT spirinpavel nucleosideanalog23isopropylidene5iodouridineasnovelefficientinhibitorofhiv1