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Current State in the Development of RNAi Self-Assembled Nanostructures
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Marwa Ben Haj Salah, John J. Rossi
The Rossi group designed a “sticky bridge” to attach an siRNA to a single cell-internalizing aptamer that binds to glycoprotein gp120 for Human Immunodeficiency Virus HIV-1 therapy (Zhou et al., 2009). Briefly, the envelope glycoprotein of HIV consists of an exterior glycoprotein (gp120) and a trans-membrane domain (gp41). HIV-1 entry depends on the interaction of gp120 with the immune cell receptor CD4 and other cell surface receptors of the chemokine receptor family (Dalgleish et al., 1984). After the binding to CD4, a cascade of conformational changes in gp120 and gp41 leads to the fusion of the viral membrane with the host membrane CD40 resulting in the successful penetration of the viral genetic material (Allan et al., 1985). Therefore, gp120 is considered a clinically relevant target for anti-HIV therapy. One approach is to design small molecules that interfere with gp120/CD4 interaction blocking virus entry and replication (Tran et al., 2011).
Anti-HIV Agents
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
HIV enters into a cell by following a few steps: HIV gp120 is binding to the CD4 receptor.HIV gp120 suffers a conformational change, which increases its affinity for a co-receptor and exposes HIV gp41.HIV gp120 binds to a co-receptor – either CCR5 or CXCR4.HIV gp41 penetrates the HIV lipid membrane and the T-cell membrane.The viral core – the capsid is entering into the cell.
PPH-Based Dendrimers as HIV Entry Inhibitors
Published in Anne-Marie Caminade, Cédric-Olivier Turrin, Jean-Pierre Majoral, Phosphorus Dendrimers in Biology and Nanomedicine, 2018
Cedric-Olivier Turrin, Muriel Blanzat
Considering HIV as a cellular pathology, rather than a viral pathology, the approach would consist in destroying or curing HIV-infected cells. Targeting HIV-infected cells can be performed by targeting gp120, expressed on the surface of HIV as well as HIV- infected cells. This strategy has been developed by Bronshtein et al. with CCR5-conjugated cell derived liposomes, which naturally bind viral glycoprotein gp120 [125]. The authors have proved that these CCR5-derived liposomes can specifically bind and fuse with their target cells and subsequently deliver their content into the infected cells leading to their destruction. First in vitro efficacy results of such system were obtained using EDTA as an encapsulated drug, which also significantly reduces the viability of controls. Although the selectivity of this drug could be improved, the in vitro biological tests validated the approach of using drug-delivery systems bearing CCR5 moieties to specifically target HIV-infected cells. With regard to the affinity of GalCer analogs with gp120, this strategy was also considered with catanionic vesicles bearing GalCer moieties on their surface [126]. As preliminary results in that direction, Mauroy et al. managed to form GalCer-derived catanionic vesicles capable of encapsulating active principles of various hydrophilicities and using different cellular uptake pathways to deliver them [123]. Especially, the authors could take advantage of the ability of these systems to fuse with cell membranes to specifically deliver anti-HIV drugs inside HIV-infected cells.
Optimal control in a multi-pathways HIV-1 infection model: a comparison between mono-drug and multi-drug therapies
Published in International Journal of Control, 2021
Chittaranjan Mondal, Debadatta Adak, Nandadulal Bairagi
Transmission of HIV-1 within a host may be possible through two modes, viz. cell-free mode and cell-to-cell mode (Hübner et al., 2009; Iwami et al., 2015; Zhong, Agosto, Munro, & Mothes, 2013). In cell-free transmission mode, free plasma virus infects the healthy cells. In this transmission process, a virus is attached to the receptor and co-receptor of healthy cell with gp120 spikes and join the host cell with the help of gp41 protein of HIV. Neutralizing antibodies can significantly affect this binding process (Zhong, Agosto, Ilinskaya, et al., 2013). After successful viral entry, the virus life cycle is completed using the host cell's machineries. First, viral RNA is transcribed into DNA with the help of reverse transcriptase enzyme of virus and it is then integrated into cell's chromosome with the help of integrase enzyme. Using the enzyme RNA polymease of the host cell, HIV makes messenger RNA and long chains of viral particle are produced using the host's enzyme. The viral protease enzyme then cuts the long chains of HIV proteins into smaller individual proteins. At the final stage, newly formed virus particles are released through cell lysis (Adamson & Freed, 2007).