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HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, randomized, double-blind, dose-escalation, placebo-controlled first-in-human trial of the HIV-1 V2-glycan-specific antibody PGDM1400 alone or in combination with the V3-glycan-specific antibody PGT121 in 24 adults without HIV in part 1, as well as a multi-center, open-label trial of the combination of PGDM1400, PGT121 and the CD4-binding-site antibody VRC07-523LS in five viremic adults living with HIV not on antiretroviral therapy (ART) in part 2 ( NCT03205917 ). The primary endpoints were safety, tolerability and pharmacokinetics for both parts and antiviral activity among viremic adults living with HIV and not on ART for part 2 of the study. The secondary endpoints were changes in CD4 T cell counts and development of HIV-1 sequence variations associated with PGDM1400, PGT121 and VRC07-523LS resistance in part 2. Intravenously administered PGDM1400 was safe and well-tolerated at doses up to 30 mg kg and when given in combination with PGT121 and VRC07-523LS. A single intravenous infusion of 20 mg kg of each of the three antibodies reduced plasma HIV RNA levels in viremic individuals by a maximum mean of 2.04 log copies per ml; however, viral rebound occurred in all participants within a median of 20 days after nadir. Rebound viruses demonstrated partial to complete resistance to PGDM1400 and PGT121 in vitro, whereas susceptibility to VRC07-523LS was preserved. Viral rebound occurred despite mean VRC07-523LS serum concentrations of 93 µg ml. The trial met the pre-specified endpoints. Our data suggest that future bNAb combinations likely need to achieve broad antiviral activity, while also maintaining high serum concentrations, to mediate viral control.
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http://dx.doi.org/10.1038/s41591-022-01815-1 | DOI Listing |
Appl Microbiol Biotechnol
December 2024
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China.
Nonstructural protein 3C, a master protease of Picornaviridae, plays a critical role in viral replication by directly cleaving the viral precursor polyprotein to form the viral capsid protein and antagonizing the host antiviral response. Additionally, 3C protease, as a tool enzyme, is involved in regulating polyprotein expression. Here, the 3C mutant gene (3Cm), fused with a small ubiquitin-like modifier (SUMO) tag at the N-terminal and featuring a mutation at position 127, was inserted into the cold-shock plasmid pCold of Escherichia coli for expression.
View Article and Find Full Text PDFThe development of effective antivirals is of great importance due to the threat associated with the rapid spread of viral infections. The accumulation of data in scientific publications and in databases of biologically active compounds provides an opportunity to extract specific information about interactions between chemicals and their viral and host targets. This information can be used for elucidation of knowledge about potential antiviral activity of chemical compounds, their side effects and toxicities.
View Article and Find Full Text PDFArh Hig Rada Toksikol
December 2024
1University of Belgrade Faculty of Pharmacy, Department of Pathobiology, Belgrade, Serbia.
Medicinal mushroom extracts, i.e. their dried biomass, have long been known as sources of bioactive compounds with positive effects on the human health.
View Article and Find Full Text PDFFront Pharmacol
December 2024
School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, China.
Natural products isolated from have attracted considerable attention from the chemical community due to their unique structures and promising anti-HIV activities. Recent progresses in the isolation and bioactivity studies for these natural molecules were summarized comprehensively. From the 23 previously uncharacterized compounds isolated from the plant , litseaverticillol B demonstrated the most potent anti-HIV activity , with IC ranging from 2 to 3 μg/mL.
View Article and Find Full Text PDFFood Chem X
December 2024
College of Engineering in Jiangxi Agricultural University, Jiangxi Key Laboratory of Modern Agricultural Equipment Jiangxi Province, Nanchang 330045, China.
is widely used as healthy food and herbal medicine for its anti-inflammatory, analgesic, antihypertensive, and antiviral functions. The drying behavior and physicochemical quality of were studied to evaluate its adaptability under four drying techniques: hot air drying (HAD), medium-and short-wave infrared drying (MSWID), pulsed vacuum drying (PVD), and radio frequency-HAD (RF-HAD). Compared with HAD and MSWID, PVD and RF-HAD can form beneficial microporous channels for moisture migration inside , thus shortening drying time by 32.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!