Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection

Gentile, Ivan; Buonomo, Antonio Riccardo; Zappulo, Emanuela; Minei, Giuseppina; Morisco, Filomena; Borrelli, Francesco; Coppola, Nicola; Borgia, Guglielmo

doi:10.2147/tcrm.s66731

Cited by 35 publications

(25 citation statements)

References 82 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To induce phosphorylation of eIF2α, we engineered the kinase domain of the eIF2α kinase protein 135 kinase RNA-activated (PKR), to harbor a recognition site (NS5A/B) for a recombinant non-structural protein 3/4 136 (NS3/4) protease, which can be chemically inhibited with Asunaprevir (ASV) 19,20 (Fig. 1a).…”

Section: A Chemogenetic Resource For Cell Type-specific Protein Synthmentioning

confidence: 99%

Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory

Shrestha

Ayata

Herrero-Vidal

et al. 2019

Preprint

View full text Add to dashboard Cite

46Translational control of memory processes is a tightly regulated process where the coordinated interaction and 47 modulation of translation factors provides a permissive environment for protein synthesis during memory 48 formation. Existing methods used to block translation lack the spatiotemporal precision to investigate cell-49 specific contributions to consolidation of long-term memories. Here, we have developed a novel chemogenetic 50 mouse resource for cell type-specific and drug-inducible protein synthesis inhibition (ciPSI) that utilizes an 51 engineered version of the catalytic kinase domain of dsRNA-activated protein (PKR). ciPSI allows rapid and 52 reversible phosphorylation of eIF2α causing a block on general translation by 50% in vivo. Using this resource, 53 we discovered that temporally structured pan-neuronal protein synthesis is required for consolidation of long-54 term auditory threat memory. Targeted protein synthesis inhibition in CamK2α expressing glutamatergic 55 neurons in lateral amygdala (LA) impaired long-term memory, which was recovered with artificial chemogenetic 56 reactivation at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eIF2α in 57 CamK2α positive neurons in LA enhanced memory strength, but was accompanied with reduced memory 58 fidelity and behavior inflexibility. Our findings provide evidence for a finely tuned translation program during 59 consolidation of long-term threat memories. Introduction 82Memory is the capacity of an organism to encode, store, and retrieve information, and often guides the 83 action of the organism towards a better survival outcome. Aversive life-threatening events often lead to long-84 term associative memories between the environment in which those events were experienced in and the 85 threat, such that a salient cue from the event when presented again can elicit species-specific defensive 86 behaviors. Pavlovian cued threat conditioning is a useful experimental paradigm for understanding the 87 biological substrates of an associative threat memory, in which a neutral cue (e.g. light or tone) co-presented 88 with an innately aversive stimulus (e.g. air puff or footshock) elicits a defensive response such as freezing by a 89 repeat presentation by itself 1 . Cued threat conditioning is particularly amenable to studying memory 90 consolidation process because one-trial training is sufficient to form a persistent long-term memory and a 91 unimodal cue can be used for memory retrieval. Long-term aversive memories are thought to recruit a 92 distributed network of neurons across the brain, including subnuclei within amygdala, hippocampus, thalamus, 93 as well as the neocortex, depending on the brain state, cue complexity, and the sensory pathways engaged 2, 3 . 94Lateral amygdala is the central sensory gateway for the amygdaloid complex and is crucially engaged both in 95 the processing and storage of the associative aversive memories 4, 5, 6 . 97Decades of studies have reported that consolidation of long-te...

show abstract

Section: A Chemogenetic Resource For Cell Type-specific Protein Synthmentioning

confidence: 99%

Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory

Shrestha

Ayata

Herrero-Vidal

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Significant safety issues associated with asunaprevir are generally limited to mild increases in aminotransferase levels, occasionally accompanied by elevations in mean plasma bilirubin. The precise mechanisms by which these hematological alterations occur have yet to be elucidated …”

Section: Adverse Events Of Daa Combination Therapiesmentioning

confidence: 99%

“…The discovery and subsequent development of direct‐acting anti‐virals (DAAs) heralded a marked improvement in rates of sustained virological response as well as quality of life . New anti‐virals have been evaluated as add‐on therapies to either pegylated interferon and ribavirin or, more recently, as all‐oral DAA combination regimens, with interferon‐based therapy now largely being eliminated from the armamentarium of HCV management …”

Section: Introductionmentioning

confidence: 99%

Review article: safety and tolerability of direct‐acting anti‐viral agents in the new era of hepatitis C therapy

Banerjee

Reddy

2016

Aliment Pharmacol Ther

134

120

View full text Add to dashboard Cite

show abstract

“…The interest in anti-fibrotic therapeutic or preventive agents has recently risen due to the availability of a new class of DAA against HCV. Whereas the clinical efficacy of these brand new medications has been widely demonstrated in eradicating HCV infection [2,[122][123][124][125][126][127][128], little is known about their effects on liver fibrosis and a significant histological improvement of cirrhosis with antiviral agents is probably unfeasible.…”

Section: Discussionmentioning

confidence: 99%

The role of curcumin in liver diseases

Buonomo¹,

Scotto²,

Nappa³

et al. 2019

aoms

Self Cite

View full text Add to dashboard Cite

A b s t r a c tChronic liver diseases are a major medical problem worldwide. Despite the availability of etiologic-specific treatments for several liver diseases, no drug or medication is available for the regression of hepatic fibrosis and cirrhosis. Curcumin is a natural compound extractable from turmeric. Several studies have uncovered its role in the modulation of biological mechanisms involved in liver injury. The best known biological effect of curcumin is the interaction with different pathways involved in the development of liver fibrosis, as shown in both in vitro and in vivo models of chronic liver injury. In pre-clinical studies, curcumin was also effective in decreasing alcohol-, glucose-and hepatitis C virus (HCV)-related liver injury, as well as HCV replication in hepatocytes. These data make curcumin a potential therapeutic agent for regression of fibrosis and cirrhosis, especially in the setting of HCV infection that can be easily eradicated thanks to the availability of several direct-acting antivirals.

show abstract

Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection

Cited by 35 publications

References 82 publications

Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory

Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory

Review article: safety and tolerability of direct‐acting anti‐viral agents in the new era of hepatitis C therapy

The role of curcumin in liver diseases

Contact Info

Product

Resources

About