Search results for "Viral Replication"

2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.

2004

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10–40 nM concentrations with minimal cytotoxicity. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic N…

Non-local multiscale approach for the impact of go or grow hypothesis on tumour-viruses interactions

2021

International audience; We propose and study computationally a novel non-local multiscale moving boundary mathematical model for tumour and oncolytic virus (OV) interactions when we consider the go or grow hypothesis for cancer dynamics. This spatio-temporal model focuses on two cancer cell phenotypes that can be infected with the OV or remain uninfected, and which can either move in response to the extracellular-matrix (ECM) density or proliferate. The interactions between cancer cells, those among cancer cells and ECM, and those among cells and OV occur at the macroscale. At the micro-scale, we focus on the interactions between cells and matrix degrading enzymes (MDEs) that impact the mov…

Parvovirus induced alterations in nuclear architecture and dynamics.

2009

The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after ph…

Role of mitochondria in parvovirus pathology.

2014

Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV) associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by rep…

Inactivation of an Enveloped Virus by Immobilized Antimicrobial Peptides.

2021

Infections caused by viruses are difficult to treat due to their life cycle, which depends on the replication machinery of the respective host cells. Commonly used antiviral strategies are based upon the application of, e.g., entry inhibitors and other compounds that interfere with virus replication. Besides possible side effects, the rapid occurrence of viral resistance poses a great challenge. Antimicrobial peptides (AMPs), as a component of the innate immunity, are able to kill bacteria and fungi and, in addition, may inactivate enveloped viruses. Many AMPs exert their biological function by impairing microbial and viral membranes. As a result, membrane integrity is lost, leading to bact…

2015

ABSTRACT Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC 50 s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither…

Cost of host radiation in an RNA virus.

2000

Abstract Although host radiation allows a parasite to expand its ecological niche, traits governing the infection of multiple host types can decrease fitness in the original or alternate host environments. Reasons for this reduction in fitness include slower replication due to added genetic material or modifications, fitness trade-offs across host environments, and weaker selection resulting from simultaneous adaptation to multiple habitats. We examined the consequences of host radiation using vesicular stomatitis virus (VSV) and mammalian host cells in tissue culture. Replicate populations of VSV were allowed to evolve for 100 generations on the original host (BHK cells), on either of two …

Calpain 1 and 2 Are Required for RNA Replication of Echovirus 1▿

2007

ABSTRACT Calpains are calcium-dependent cysteine proteases that degrade cytoskeletal and cytoplasmic proteins. We have studied the role of calpains in the life cycle of human echovirus 1 (EV1). The calpain inhibitors, including calpeptin, calpain inhibitor 1, and calpain inhibitor 2 as well as calpain 1 and calpain 2 short interfering RNAs, completely blocked EV1 infection in the host cells. The effect of the inhibitors was not specific for EV1, because they also inhibited infection by other picornaviruses, namely, human parechovirus 1 and coxsackievirus B3. The importance of the calpains in EV1 infection also was supported by the fact that EV1 increased calpain activity 3 h postinfection. …

Abscisic Acid Connects Phytohormone Signaling with RNA Metabolic Pathways and Promotes an Antiviral Response that Is Evaded by a Self-Controlled RNA …

2020

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Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

2016

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level o…