Jay Trivedi1,2, Dinesh Mahajan3, Russell J Jaffe2, Arpan Acharya2, Debashis Mitra4,5, Siddappa N Byrareddy6,7,8. 1. National Centre for Cell Science, Pune University Campus, Pune, Maharashtra, India. 2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. 3. Drug Discovery Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad, Haryana, India. 4. National Centre for Cell Science, Pune University Campus, Pune, Maharashtra, India. dmitra@nccs.res.in. 5. Centre for DNA Fingerprinting and Diagnostics, Uppal Telangana state, Hyderabad, India. dmitra@nccs.res.in. 6. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. sid.byrareddy@unmc.edu. 7. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA. sid.byrareddy@unmc.edu. 8. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. sid.byrareddy@unmc.edu.
Abstract
PURPOSE OF THE REVIEW: The complex multistep life cycle of HIV allows it to proliferate within the host and integrate its genome in to the host chromosomal DNA. This provirus can remain dormant for an indefinite period. The process of integration, governed by integrase (IN), is highly conserved across the Retroviridae family. Hence, targeting integration is not only expected to block HIV replication but may also reveal new therapeutic strategies to treat HIV as well as other retrovirus infections. RECENT FINDINGS: HIV integrase (IN) has gained attention as the most promising therapeutic target as there are no equivalent homologues of IN that has been discovered in humans. Although current nano-formulated long-acting IN inhibitors have demonstrated the phenomenal ability to block HIV integration and replication with extraordinary half-life, they also have certain limitations. In this review, we have summarized the current literature on clinically established IN inhibitors, their mechanism of action, the advantages and disadvantages associated with their therapeutic application, and finally current HIV cure strategies using these inhibitors.
PURPOSE OF THE REVIEW: The complex multistep life cycle of HIV allows it to proliferate within the host and integrate its genome in to the host chromosomal DNA. This provirus can remain dormant for an indefinite period. The process of integration, governed by integrase (IN), is highly conserved across the Retroviridae family. Hence, targeting integration is not only expected to block HIV replication but may also reveal new therapeutic strategies to treat HIV as well as other retrovirus infections. RECENT FINDINGS:HIVintegrase (IN) has gained attention as the most promising therapeutic target as there are no equivalent homologues of IN that has been discovered in humans. Although current nano-formulated long-acting IN inhibitors have demonstrated the phenomenal ability to block HIV integration and replication with extraordinary half-life, they also have certain limitations. In this review, we have summarized the current literature on clinically established IN inhibitors, their mechanism of action, the advantages and disadvantages associated with their therapeutic application, and finally current HIV cure strategies using these inhibitors.
Entities:
Keywords:
HIV integration; Integrase inhibitors; Latent provirus; Retroviridae; Therapeutic application
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