Targeting the HIV RNA genome: high-hanging fruit only needs a longer ladder

Current Topics in Microbiology and Immunology
Stuart F J Le Grice

Abstract

Small molecules targeting the enzymes responsible for human immunodeficiency virus (HIV) maturation, DNA synthesis and its subsequent chromosomal integration as ribonucleotide-free double-stranded DNA remain the mainstay of combination antiretroviral therapy. For infected individuals harboring drug-susceptible virus, this approach has afforded complete or near-complete viral suppression. However, in the absence of a curative strategy, the predictable emergence of drug-resistant variants requires continued development of improved antiviral strategies, inherent to which is the necessity of identifying novel targets. Regulatory elementsRegulatory elements that mediate transcription, translation, nucleocytoplasmic transport, dimerization, packaging and reverse transcription of the (+) strand RNA genomeRNA genome should now be considered viable targets for small molecule, peptide- and oligonucleotide-based therapeuticsTherapeutics . Where target specificity and cellular penetration and toxicity have been the primary obstacle to successful "macromolecule therapeutics", this chapter summarizes (a) novel approaches targeting RNA motifs whose three-dimensional structure is critical for biological function and consequently may be less pr...Continue Reading

Citations

Aug 25, 2015·Frontiers in Public Health·Alexey Karetnikov
Oct 25, 2016·ACS Chemical Biology·Brian P CharretteThomas Hermann
Dec 14, 2016·ACS Chemical Biology·Colleen M ConnellyJohn S Schneekloth
Jan 23, 2018·Frontiers in Microbiology·Chun Shen Lim, Chris M Brown
Feb 6, 2020·Journal of Biomolecular Structure & Dynamics·Ruby Srivastava
Jan 17, 2020·Viruses·Chringma Sherpa, Stuart F J Le Grice
Nov 17, 2020·Advanced Healthcare Materials·Yi WangDavid R Nisbet
Dec 23, 2016·Journal of Medicinal Chemistry·Fardokht A AbulwerdiJohn S Schneekloth
Jan 13, 2018·Biochemistry·Michelle H MoonJohn S Schneekloth

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Methods Mentioned

BETA
antisense oligonucleotides
NMR
isothermal titration calorimetry
fluorescence
electrophoretic mobility
footprinting
myristoylation
X-ray

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