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Virus Res. 2014 Nov 26;193:135-43. doi: 10.1016/j.virusres.2014.07.004. Epub 2014 Jul 12.

Advances in targeting nucleocapsid-nucleic acid interactions in HIV-1 therapy.

Author information

1
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: betorbet@scripps.edu.

Abstract

The continuing challenge of HIV-1 treatment resistance in patients creates a need for the development of new antiretroviral inhibitors. The HIV nucleocapsid (NC) protein is a potential therapeutic target. NC is necessary for viral RNA packaging and in the early stages of viral infection. The high level of NC amino acid conservation among all HIV-1 clades suggests a low tolerance for mutations. Thus, NC mutations that could arise during inhibitor treatment to provide resistance may render the virus less fit. Disruption of NC function provides a unique opportunity to strongly dampen replication at multiple points during the viral life cycle with a single inhibitor. Although NC exhibits desirable features for a potential antiviral target, the structural flexibility, size, and the presence of two zinc fingers makes small molecule targeting of NC a challenging task. In this review, we discuss the recent advances in strategies to develop inhibitors of NC function and present a perspective on potential novel approaches that may help to overcome some of the current challenges in the field.

KEYWORDS:

HIV-1; Inhibitors; Nucleocapsid protein; RNA

PMID:
25026536
PMCID:
PMC4252855
DOI:
10.1016/j.virusres.2014.07.004
[Indexed for MEDLINE]
Free PMC Article

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