Skip to content

Research at St Andrews

Protease mediated maturation of HIV: Inhibitors of protease and the maturation process

Research output: Contribution to journalReview articlepeer-review

DOI

Open Access permissions

Open

Abstract

Protease-mediated maturation of HIV-1 virus particles is essential for virus infectivity. Maturation occurs concomitant with immature virus particle release and is mediated by the viral protease (PR), which sequentially cleaves the Gag and Gag-Pol polyproteins into mature protein domains. Maturation triggers a second assembly event that generates a condensed conical capsid core. The capsid core organizes the viral RNA genome and viral proteins to facilitate viral replication in the next round of infection. The fundamental role of proteolytic maturation in the generation of mature infectious particles has made it an attractive target for therapeutic intervention. Development of small molecules that target the PR active site has been highly successful and nine protease inhibitors (PIs) have been approved for clinical use. This review provides an overview of their development and clinical use together with a discussion of problems associated with drug-resistance. The second-half of the review discusses a novel class of antiretroviral drug termed maturation inhibitors, which target cleavage sites in Gag not PR itself. The review focuses on bevirimat (BVM) the first-in-class maturation inhibitor; its mechanism of action and the implications of naturally occurring polymorphisms that confer reduced susceptibility to BVM in phase II clinical trials.
Close

Details

Original languageEnglish
Article number604261
Number of pages13
JournalMolecular Biology International
Volume2012 Special Issue: Host-Pathogen Interactions
DOIs
Publication statusPublished - 2012

    Research areas

  • HIV, Protease, Inhibitors, Bevirimat

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Antiviral agent: discovery to resistance

    Adamson, C. S., 7 Apr 2020, In: Viruses. 12, 4, 3 p., 406.

    Research output: Contribution to journalEditorial

  2. Bright and early: inhibiting human cytomegalovirus by targeting major immediate-early gene expression or protein function

    Adamson, C. S. & Nevels, M. M., 16 Jan 2020, In: Viruses. 12, 1, 41 p., 110.

    Research output: Contribution to journalReview articlepeer-review

  3. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice

    Vasou, A., Paulus, C., Narloch, J., Gage, Z. O., Rameix-Welti, M-A., Eléouët, J-F., Nevels, M., Randall, R. E. & Adamson, C. S., Feb 2018, In: Antiviral Research. 150, p. 79-92

    Research output: Contribution to journalArticlepeer-review

  4. Identification of novel inhibitors of the type I interferon induction pathway using cell-based high-throughput screening

    Gage, Z. O., Vasou, A., Gray, D., Randall, R. E. & Adamson, C. S., Oct 2016, In: Journal of Biomolecular Screening. 21, 9, p. 978-988 11 p.

    Research output: Contribution to journalArticlepeer-review

  5. Structure-activity relationships of the Human Immunodeficiency Virus type 1 maturation inhibitor PF-46396

    Murgatroyd, C., Pirrie, L., Tran, F., Smith, T. K., Westwood, N. J. & Adamson, C. S., Sep 2016, In: Journal of Virology. 90, 18, p. 8181-8197 17 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

ID: 23262888

Top