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Identification of potent maturation inhibitors against HIV-1 clade C
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic.
- Subjects :
- 0301 basic medicine
Infectivity
Multidisciplinary
Sequence Homology, Amino Acid
Anti-HIV Agents
Maturation inhibitor
Sequence analysis
Drug resistance
Group-specific antigen
Biology
Virology
Article
Virus
Cell Line
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
chemistry
Drug Resistance, Viral
HIV-1
Humans
Amino Acid Sequence
Clade
Bevirimat
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....48920e45cfb5abec9184e8898f30849d