Targeting RNA-protein interactions within the human immunodeficiency virus type 1 lifecycle

Biochemistry
Neil M BellShankar Balasubramanian

Abstract

RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Ψ), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and Ψ. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by ¹H NMR spectroscopy.

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Citations

Jul 7, 2015·Biochimica Et Biophysica Acta·Jozef NahalkaKlaudia Talafova
Jul 16, 2014·Virus Research·Divita Garg, Bruce E Torbett
Oct 16, 2019·Organic & Biomolecular Chemistry·Neeraj N PatwardhanAmanda E Hargrove
May 19, 2020·SLAS Discovery·Hafeez S HaniffHelen L Lightfoot
Aug 14, 2018·Nucleic Acids Research·Brittany S MorganAmanda E Hargrove
Jan 25, 2019·Scientific Reports·Branko StefanovicLela Stefanovic
Jul 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Pengfei DingMichael F Summers
Aug 12, 2017·MedChemComm·Neeraj N PatwardhanAmanda E Hargrove
Oct 4, 2020·Viruses·Patricia S BoydSaif Yasin
Jan 23, 2021·RSC Medicinal Chemistry·G PadroniA E Hargrove
Jul 4, 2021·Trends in Pharmacological Sciences·William J MartinMarco Marcia

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
circular dichroism
NMR
gel filtration
transfection
Fluorescence

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