Journal article
The discovery and design of novel HIV-1 capsid modulators and future perspectives
Expert opinion on drug discovery, v 18(1), 5
02 Jan 2023
PMID: 36480372
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although combination antiretroviral therapy (cART) has achieved significant success in treating HIV, the emergence of multidrug-resistant viruses and cumulative medication toxicity make it necessary to find new classes of antiretroviral agents with novel mechanisms of action. With high sequence conservation, the HIV-1 capsid (CA) protein has attracted attention as a prospective therapeutic target due to its crucial structural and regulatory functions in the HIV-1 replication cycle.
Herein, the authors provide a cutting-edge overview of current advances in the design and discovery of CA modulators, PF74, GS-6207 and their derivativeswhich targets a therapeutically attractive NTD-CTD interprotomer pocket within the hexameric configuration of HIV-1 CA. The discovery and development of these compounds, and derivatives thereof, have provided valuable information for the design of second-generation CA-targeting antivirals.
Despite some successes in designing and discovering HIV-1 CA modulators, more studies are required to decipher which chemical groups confer specific desirable properties. The future of CA-modulating compounds may lie in covalent inhibition and the creation of proteolysis-targeting chimeras (PROTACs). Moreover, biological interrogation of the process of CA uncoating, virus-host interactions, and studies on the lattice-binding restriction factors may improve our knowledge of HIV-1 CA and support the design of new antiviral agents.
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Details
- Title
- The discovery and design of novel HIV-1 capsid modulators and future perspectives
- Creators
- Dang Ding - Shandong UniversityShujing Xu - Shandong UniversityXujie Zhang - Shandong UniversityXiangyi Jiang - Shandong UniversitySimon Cocklin - Drexel UniversityAlexej Dick - Drexel UniversityPeng Zhan - Shandong UniversityXinyong Liu - Shandong University
- Publication Details
- Expert opinion on drug discovery, v 18(1), 5
- Publisher
- Taylor & Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000899059000001
- Scopus ID
- 2-s2.0-85144106204
- Other Identifier
- 991021230007404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy