C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors
Abstract Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorp...
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BMC
2025-01-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-025-02635-8 |
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| author | K. C. Yuvraj Aradhana Singh Sayantani Datta Ritika Das Pranjal Raj Saxena Subash Chapagain T. J. Nitz Carl Wild Ritu Gaur |
| author_facet | K. C. Yuvraj Aradhana Singh Sayantani Datta Ritika Das Pranjal Raj Saxena Subash Chapagain T. J. Nitz Carl Wild Ritu Gaur |
| author_sort | K. C. Yuvraj |
| collection | DOAJ |
| description | Abstract Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM. Second generation BVM analogs with modifications at C-28 position gained potent activity against HIV-1 subtype C. In this study, we have evaluated the efficacy of nine second-generation MIs (BVM analogs) with varying length of C28 carbon linker against HIV-1 subtype B and C. Increasing the length of carbon linker decreased their activity against both subtypes. These MIs were also active against integrase inhibitor-resistant viruses and protease inhibitor-resistant viruses. Our data has provided vital information that in addition to the nature of the functional group at C28 position of the MI, the length of linker contributes significantly to its activity. The shorter the length, the better the activity of MIs. These results will further pave way for design of novel and potent MIs. |
| format | Article |
| id | doaj-art-814f2ef8f72048eba5299a34bbb3d019 |
| institution | Kabale University |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-814f2ef8f72048eba5299a34bbb3d0192025-02-02T12:08:37ZengBMCVirology Journal1743-422X2025-01-012211710.1186/s12985-025-02635-8C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitorsK. C. Yuvraj0Aradhana Singh1Sayantani Datta2Ritika Das3Pranjal Raj Saxena4Subash Chapagain5T. J. Nitz6Carl Wild7Ritu Gaur8Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)DFH PharmaDFH PharmaVirology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU)Abstract Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM. Second generation BVM analogs with modifications at C-28 position gained potent activity against HIV-1 subtype C. In this study, we have evaluated the efficacy of nine second-generation MIs (BVM analogs) with varying length of C28 carbon linker against HIV-1 subtype B and C. Increasing the length of carbon linker decreased their activity against both subtypes. These MIs were also active against integrase inhibitor-resistant viruses and protease inhibitor-resistant viruses. Our data has provided vital information that in addition to the nature of the functional group at C28 position of the MI, the length of linker contributes significantly to its activity. The shorter the length, the better the activity of MIs. These results will further pave way for design of novel and potent MIs.https://doi.org/10.1186/s12985-025-02635-8Maturation inhibitorsC-28 Linker lengthHIV-1 Subtype B and CHIV-1 maturation |
| spellingShingle | K. C. Yuvraj Aradhana Singh Sayantani Datta Ritika Das Pranjal Raj Saxena Subash Chapagain T. J. Nitz Carl Wild Ritu Gaur C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors Virology Journal Maturation inhibitors C-28 Linker length HIV-1 Subtype B and C HIV-1 maturation |
| title | C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors |
| title_full | C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors |
| title_fullStr | C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors |
| title_full_unstemmed | C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors |
| title_short | C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors |
| title_sort | c 28 linker length modulates the activity of second generation hiv 1 maturation inhibitors |
| topic | Maturation inhibitors C-28 Linker length HIV-1 Subtype B and C HIV-1 maturation |
| url | https://doi.org/10.1186/s12985-025-02635-8 |
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