Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression
<b>Background</b>: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P...
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2024-12-01
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| author | Sharif Karim Sayyed Marzuqa Quraishi D. S. Prabakaran Balaji Chandrasekaran Thiyagarajan Ramesh Satish Kumar Rajasekharan Chaitany Jayprakash Raorane Tareeka Sonawane Vinothkannan Ravichandran |
| author_facet | Sharif Karim Sayyed Marzuqa Quraishi D. S. Prabakaran Balaji Chandrasekaran Thiyagarajan Ramesh Satish Kumar Rajasekharan Chaitany Jayprakash Raorane Tareeka Sonawane Vinothkannan Ravichandran |
| author_sort | Sharif Karim Sayyed |
| collection | DOAJ |
| description | <b>Background</b>: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P), thereby establishing its dual-targeting capability. <b>Methods</b>: The inhibitory activity of Zinc C295 against 3′P was evaluated using a modified in vitro assay adapted from our earlier ST inhibition studies. Molecular docking and molecular dynamics simulations were employed to analyse Zinc C295’s interactions with the 3′P allosteric site of HIV-1 integrase. <b>Results</b>: Zinc C295 demonstrated significant inhibition of HIV-1 integrase 3′P activity in in vitro assays (IC50 = 4.709 ± 0.97 µM). Computational analyses revealed key interactions of Zinc C295 within the enzyme’s allosteric site, providing insights into its dual inhibitory mechanism. <b>Conclusions</b>: Zinc C295’s dual inhibition of HIV-1 integrase ST and 3′P establishes it as a promising candidate for next-generation ART. Its dual-action mechanism may offer potential advantages in enhancing treatment efficacy and addressing drug resistance. Further studies are warranted to evaluate its therapeutic potential in clinical settings. |
| format | Article |
| id | doaj-art-0e56e0ba4ea6445baa2c4781d38a9535 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-0e56e0ba4ea6445baa2c4781d38a95352025-01-24T13:45:04ZengMDPI AGPharmaceuticals1424-82472024-12-011813010.3390/ph18010030Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing SuppressionSharif Karim Sayyed0Marzuqa Quraishi1D. S. Prabakaran2Balaji Chandrasekaran3Thiyagarajan Ramesh4Satish Kumar Rajasekharan5Chaitany Jayprakash Raorane6Tareeka Sonawane7Vinothkannan Ravichandran8Amity Institute of Biotechnology, Amity University Maharashtra, Mumbai 410206, Maharashtra, IndiaAmity Institute of Biotechnology, Amity University Maharashtra, Mumbai 410206, Maharashtra, IndiaDepartment of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77845, USADepartment of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, IndiaSchool of Chemical Engineering, Yeungman University, Gyeongsan 38541, Republic of KoreaAmity Institute of Biotechnology, Amity University Maharashtra, Mumbai 410206, Maharashtra, IndiaAmity Institute of Biotechnology, Amity University Maharashtra, Mumbai 410206, Maharashtra, India<b>Background</b>: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P), thereby establishing its dual-targeting capability. <b>Methods</b>: The inhibitory activity of Zinc C295 against 3′P was evaluated using a modified in vitro assay adapted from our earlier ST inhibition studies. Molecular docking and molecular dynamics simulations were employed to analyse Zinc C295’s interactions with the 3′P allosteric site of HIV-1 integrase. <b>Results</b>: Zinc C295 demonstrated significant inhibition of HIV-1 integrase 3′P activity in in vitro assays (IC50 = 4.709 ± 0.97 µM). Computational analyses revealed key interactions of Zinc C295 within the enzyme’s allosteric site, providing insights into its dual inhibitory mechanism. <b>Conclusions</b>: Zinc C295’s dual inhibition of HIV-1 integrase ST and 3′P establishes it as a promising candidate for next-generation ART. Its dual-action mechanism may offer potential advantages in enhancing treatment efficacy and addressing drug resistance. Further studies are warranted to evaluate its therapeutic potential in clinical settings.https://www.mdpi.com/1424-8247/18/1/30drug resistancedual inhibitionHIV-1 integrase inhibitorsin vitro assaysmolecular docking simulationantiretroviral drug development |
| spellingShingle | Sharif Karim Sayyed Marzuqa Quraishi D. S. Prabakaran Balaji Chandrasekaran Thiyagarajan Ramesh Satish Kumar Rajasekharan Chaitany Jayprakash Raorane Tareeka Sonawane Vinothkannan Ravichandran Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression Pharmaceuticals drug resistance dual inhibition HIV-1 integrase inhibitors in vitro assays molecular docking simulation antiretroviral drug development |
| title | Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression |
| title_full | Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression |
| title_fullStr | Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression |
| title_full_unstemmed | Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression |
| title_short | Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression |
| title_sort | exploring zinc c295 as a dual hiv 1 integrase inhibitor from strand transfer to 3 processing suppression |
| topic | drug resistance dual inhibition HIV-1 integrase inhibitors in vitro assays molecular docking simulation antiretroviral drug development |
| url | https://www.mdpi.com/1424-8247/18/1/30 |
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