Last update 21 Nov 2024

Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

HIV prevention(DelSiTech)

Target-

Mechanism-

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication-

Originator Organization

DelSiTech Oy

Active Organization

DelSiTech Oy

Inactive Organization

Innovare R&D

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

100 Translational Medicine associated with Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

100 Patents (Medical) associated with Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

Literatures (Medical) associated with Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

01 Aug 2019·AIDSQ2 · MEDICINE

Revisiting the mechanism of enfuvirtide and designing an analog with improved fusion inhibitory activity by targeting triple sites in gp41

Q2 · MEDICINE

Article

Author: Su, Shan ; Lu, Lu ; Hua, Chen ; Pu, Jing ; Xu, Wei ; Su, Xiaojie ; Wang, Qian ; Jiang, Shibo

OBJECTIVETo revisit the mechanism of action of enfuvirtide (T20) and based on the newly defined mechanism, design an analogous peptide of T20 with improved antiviral activity.DESIGNWe compared the inhibitory activity of T20 with that of T1144 on six-helix bundle (6HB) formation at different time after coculture of HIV type 1 (HIV-1) envelope (Env)-expressing Chinese hamster ovary (CHO-Env) cells and CD4-expressing MT-2 cells at 31.5 °C and with that of T20-SF, an analogous peptide of T20 with an additional tryptophan-rich motif, on hemolysis mediated by FP-P, which contains fusion peptide and fusion peptide (FP) proximal region (FPPR), and HIV-1 infection.METHODSInhibitory activity of peptides on 6HB formation was tested in a temperature-controlled cell-cell fusion assay by flow cytometry using 6HB-specific mAb 2G8; on HIV-1 infection and fusion was assessed by p24 and cell-cell fusion assays. Interaction between different peptides or peptide and antibody was evaluated by ELISA.RESULTST20 could inhibit 6HB formation at early, but not late, stage of HIV-1 fusion, whereas T1144 was effective at both stages. T20-SF is much more effective than T20 in binding to FP-P and inhibiting infection of HIV-1, including T20-resistant strains, and FP-P-mediated hemolysis.CONCLUSIONResults suggest that T20 has a double-target mechanism, by which its N-terminal and C-terminal portions bind to N-terminal heptad repeat and FPPR, respectively. T20-SF designed based on this new mechanism exhibits significantly improved anti-HIV-1 activity because it targets the triple sites in gp41, including N-terminal heptad repeat, FPPR, and fusion peptide. Thus, this study provides clues for designing novel HIV fusion inhibitors with improved antiviral activity.

27 Mar 2016·AIDSQ2 · MEDICINE

Co-delivery of HIV-1 entry inhibitor and nonnucleoside reverse transcriptase inhibitor shuttled by nanoparticles

Q2 · MEDICINE

Article

Author: Qi, Qianqian ; Xie, Lan ; Wang, Qian ; Jiang, Shibo ; Lu, Lu ; Li, Wen ; Yu, Fei ; Su, Shan

OBJECTIVESTraditionally, the antiviral efficacy of classic cocktail therapy is significantly limited by the distinct pharmacokinetic profiles of partner therapeutics that lead to inconsistent in-vivo biodistribution. Here we developed a new cocktail-like drug delivery vehicle using biodegradable polymeric nanoparticles (NP) encapsulating nonnucleoside reverse transcriptase inhibitor (NNRTI) DAAN-14f (14f), surface-conjugated with HIV-1 fusion inhibitor T1144, designated T1144-NP-DAAN-14f (T1144-NP-14f), and aiming to achieve enhanced cellular uptake, improved antiviral activity and prolonged blood circulation time.METHODST1144-NP-14f was prepared through the emulsion/solvent evaporation technique and a maleimide-thiol coupling reaction. Particle size and morphology were determined by dynamic light scattering detection and transmission electron microscopy. Anti-HIV-1 activity was assessed by HIV-1 Env-mediated cell-cell fusion and infection by laboratory-adapted, primary, and resistant HIV-1 isolates, respectively. The in-vitro release of 14f was investigated using the equilibrium dialysis method, and the pharmacokinetic study of T1144-NP-14f was performed on Sprague-Dawley rats.RESULTST1144-NP-14f displayed a spherical shape under transmission electron microscopy observation and had a size of 117 ± 19 nm. T1144-NP-14f exhibited the strongest antiviral activity against a broad spectrum of HIV-1 strains, including NNRTI-, T1144-, or T20-resistant isolates, respectively. Both in-vitro release and in-vivo pharmacokinetic profile showed that T1144-NP-14f exhibited a sustained controlled release behavior.CONCLUSIONOur results demonstrated that the combination of entry inhibitor with NNRTI encapsulated in nanoparticles (T1144-NP-14f) was highly effective in inhibiting HIV-1 infection. This new cocktail-like drug delivery platform could serve as an effective anti-HIV-1 regimen by taking advantage of the extrinsic and intrinsic antiviral activity of individual drugs.

01 Dec 2012·RetrovirologyQ2 · MEDICINE

A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains

Q2 · MEDICINE

ArticleOA

Author: Lu Lu ; Shibo Jiang ; Chungen Pan ; W u He ; Yuan Li ; Hong Lu

AbstractBackgroundMost currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4) can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell.ResultsWe engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI), but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT.ConclusionThis bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.

100 Deals associated with Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Preclinical	FI	DelSiTech Oy	28 Jan 2023

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Long-acting controlled formulations of human immunodeficiency virus (HIV) anti-retrovirals(DelsiTech)

Overview

Basic Info

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R&D Status

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Translational Medicine

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