Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1

Current Topics in Microbiology and Immunology
Mattia MoriYves Mély

Abstract

The currently available anti-HIV-1 therapeutics is highly beneficial to infected patients. However, clinical failures occur as a result of the ability of HIV-1 to rapidly mutate. One approach to overcome drug resistance is to target HIV-1 proteins that are highly conserved among phylogenetically distant viral strains and currently not targeted by available therapies. In this respect, the nucleocapsid (NC) protein, a zinc finger protein, is particularly attractive, as it is highly conserved and plays a central role in virus replication, mainly by interacting with nucleic acids. The compelling rationale for considering NC as a viable drug target is illustrated by the fact that point mutants of this protein lead to noninfectious viruses and by the inability to select viruses resistant to a first generation of anti-NC drugs. In our review, we discuss the most relevant properties and functions of NC, as well as recent developments of small molecules targeting NC. Zinc ejectors show strong antiviral activity, but are endowed with a low therapeutic index due to their lack of specificity, which has resulted in toxicity. Currently, they are mainly being investigated for use as topical microbicides. Greater specificity may be achieved by...Continue Reading

Citations

Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mattia MoriAnastasia Karioti
Sep 25, 2017·Inorganic Chemistry·Raphael E F de PaivaNicholas P Farrell
May 22, 2020·ACS Medicinal Chemistry Letters·Stefano CiacoYves Mély
May 22, 2020·ACS Medicinal Chemistry Letters·Savina MalanconaMaurizio Botta
Dec 10, 2016·Inorganic Chemistry·Victor H F BernardesNicholas P Farrell
Dec 6, 2019·Journal of Chemical Information and Modeling·Mattia MoriAndrea Tafi
May 31, 2017·Inorganic Chemistry·Geoffrey D ShimbergSarah L J Michel

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Datasets Mentioned

BETA
K03455

Methods Mentioned

BETA
acylation
transgenic
isothermal titration calorimetry
nuclear magnetic resonance
electrophoretic mobility shift assay
X-ray
NMR
footprinting

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