Search results for "antiviral agent"
showing 10 items of 505 documents
Optimum combination therapy regimens for HIV/HCV infection
2016
HIV-HCV co-infection mostly affects intravenous drug users, in whom prevalence has tended to decrease in recent years, while it has increased in men who have sex with men, with occurrence of acute hepatitis C. Hepatitis C has a poorer prognosis in patients co-infected with HIV, as clinical progression is faster and degree of hepatic fibrosis is greater. However, optimized ARV treatment is clearly associated with slower progression to hepatic complications. Interactions between HCV and HIV drugs are numerous, which underlines the importance of pharmacological advice for HIV-treated patients before they start HCV treatment. In HIV-HCV co-infection, treatment of hepatitis C has to be offered a…
Current and future challenges in HCV: insights from an Italian experts panel
2017
Background: The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages. Methods: A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens. Results and conclusions: Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated …
Social evolution of innate immunity evasion in a virus
2019
Antiviral immunity has been studied extensively from the perspective of virus−cell interactions, yet the role of virus−virus interactions remains poorly addressed. Here, we demonstrate that viral escape from interferon (IFN)-based innate immunity is a social process in which IFN-stimulating viruses determine the fitness of neighbouring viruses. We propose a general and simple social evolution framework to analyse how natural selection acts on IFN shutdown and validate it in cell cultures and mice infected with vesicular stomatitis virus. Furthermore, we find that IFN shutdown is costly because it reduces short-term viral progeny production, thus fulfilling the definition of an altruistic tr…
In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection
2020
COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (MPRO) inhibitors that fit in the catalytic binding site of SARS CoV-2 MPRO. Several sel…
The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations
2020
Graphical abstract The inorganic physiological polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations. This discovery proposes polyphosphate as a new member of the host's antiviral innate immune defense.
Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: Inhibition kinetics and docking studies
2014
NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 μM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 μM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis…
The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy
1999
The hepatitis C virus (HCV) is a major causative agent of transfusion-acquired and sporadic non-A, non-B hepatitis worldwide. Infections most often persist and lead, in approximately 50% of all patients, to chronic liver disease. As is characteristic for a member of the family Flaviviridae, HCV has a plus-strand RNA genome encoding a polyprotein, which is cleaved co- and post-translationally into at least 10 different products. These cleavages are mediated, among others, by a virally encoded chymotrypsin-like serine proteinase located in the N-terminal domain of non-structural protein 3 (NS3). Activity of this enzyme requires NS4A, a 54-residue polyprotein cleavage product, to form a stable…
Synthesis of C-17-functionalized spongiane diterpenes: diastereoselective synthesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1, and (-)-apl…
2003
The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyldendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial (-)-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)-acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unpreced…
Virtual Combinatorial Syntheses and Computational Screening of New Potential Anti-Herpes Compounds
1999
The activity of new anti-HSV-1 chemical structures, designed by virtual combinatorial chemical synthesis and selected by a computational screening, is determined by an in vitro assay. A virtual library of phenol esters and anilides was formed from two databases of building blocks: one with carbonyl fragments and the other containing both substituted phenoxy and phenylamino fragments. The library of virtually assembled compounds was computationally screened, and those compounds which were selected by our mathematical model as active ones were finally synthesized and tested. Our antiviral activity model is a "tandem" of four linear functions of topological graph-theoretical descriptors. A giv…
Antiviral efficacy of cerium oxide nanoparticles.
2022
The authors gratefully acknowledge the financial support by the Estonian Research Council Grants (COVSG2, PRG629, PRG1496), Estonian Centre of Excellence in Research project “Advanced materials and high-technology devices for sustainable energetics, sensorics and nanoelectronics” TK141 (2014-2020.4.01.15-0011) and University of Tartu Development Fund (PLTFYARENG53). The research was partly conducted using the NAMUR+ core facility funded by projects “Center of nanomaterials technologies and research” (2014-2020.4.01.16-0123) and TT13.