Search results for "Membrane interaction"

Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

2020

Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-naive patients (5%) and the number of NS5A RASs was significantly highe…

Buccal Thin Films as Potent Permeation Enhancers for Cytisine Transbuccal Delivery

2022

Cytisine (CYT) is a powerful anti-smoking compound which could greatly benefit from transbuccal delivery because of both its unfavorable pharmacokinetics after oral administration and its intrinsic ability to permeate the buccal mucosa. This work aims to design CYT-loaded buccal thin films suitable for transbuccal drug delivery due to its capability of promoting the interaction between CYT and the buccal membrane. The solvent casting method was employed to prepare several thin films combining various excipients such as matrixing polymers, mucoadhesion agents, plasticizers and other compounds as humectants and sweeteners, component ratios and solvents. A total of 36 compositions was prepared…

Phasor-FLIM for a direct investigation of Transportan 10 interactions with model membranes

2023

Transportan 10 (TP10), a short and positive charged peptide, belonging to the family of the cell penetrating peptides has gained increasing attention for its antimicrobial and anticancer activity but also for its applications in drug delivery as it is able to translocate therapeutic molecules in cellular environment. Due to the complexity of the phenomena involved in cellular uptake and following processes, which strongly depend on the membrane lipid composition, structural details of the peptide (e.g., charge, hydrophobicity, steric hindrance) and environmental conditions, it is not easy to understand the general rules governing them. Here, we combine spectroscopic techniques and fluoresce…

Molecular mechanisms underlying proteins-membrane interaction

From endosomes onwards : membranes, lysosomes and viral capsid interactions

2009

Kirsi Pakkanen haki väitöstutkimuksessaan monitieteellisen lähestymistavan avulla uusia näkökulmia virustutkimukseen. Tutkimus tuo uutta tietoa lipidikalvojen merkityksestä viruksen ja viruksen isäntäsolun elämässä. Tutkimuksessa selvisi, että koiran parvovirus, jota tutkimuksessa käytettiin mallina parvoviruksille ja yleisemmin vaipattomille viruksille, tarvitsee tietynlaisia isäntäsolun lipidikalvojen ominaisuuksia voidakseen vapautua solunsisäisten endosomirakkuloiden sisältä. Erityisen tärkeää tässä vapautumisessa näytti olevan kalvojen juoksevuus sekä jäykkien alueiden hallittu järjestäytyminen kolesterolin avulla. Hyödyntämällä molekyylejä, lääkeaineita, jotka muuttavat kolesteroliavu…

Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release

2021

Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by fu…