39,946 results match your criteria Antiviral Chemistry & Chemotherapy[Journal]


Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells.

Viruses 2019 Apr 20;11(4). Epub 2019 Apr 20.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

Zika virus (ZIKV), an emerging flavivirus that causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barré syndrome continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of ribonucleoside analogues. Here, we synthesized and tested a small library of 13 ProTides against ZIKV in human neural stem cells. Read More

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http://dx.doi.org/10.3390/v11040365DOI Listing

Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity.

Cell 2019 Apr 16. Epub 2019 Apr 16.

Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, MA 02115, USA. Electronic address:

The conventional view posits that E3 ligases function primarily through conjugating ubiquitin (Ub) to their substrate molecules. We report here that RIPLET, an essential E3 ligase in antiviral immunity, promotes the antiviral signaling activity of the viral RNA receptor RIG-I through both Ub-dependent and -independent manners. RIPLET uses its dimeric structure and a bivalent binding mode to preferentially recognize and ubiquitinate RIG-I pre-oligomerized on dsRNA. Read More

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http://dx.doi.org/10.1016/j.cell.2019.03.017DOI Listing

Targeting host metabolism by inhibition of acetyl-Coenzyme A carboxylase reduces flavivirus infection in mouse models.

Emerg Microbes Infect 2019 ;8(1):624-636

a Department of Biotechnology , Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) , Madrid , Spain.

Flaviviruses are (re)-emerging RNA viruses strictly dependent on lipid metabolism for infection. In the search for host targeting antivirals, we explored the effect of pharmacological modulation of fatty acid metabolism during flavivirus infection. Considering the central role of acetyl-Coenzyme A carboxylase (ACC) on fatty acid metabolism, we analyzed the effect of three small-molecule ACC inhibitors (PF-05175157, PF-05206574, and PF-06256254) on the infection of medically relevant flaviviruses, namely West Nile virus (WNV), dengue virus, and Zika virus. Read More

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https://www.tandfonline.com/doi/full/10.1080/22221751.2019.1
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http://dx.doi.org/10.1080/22221751.2019.1604084DOI Listing
January 2019
1 Read

Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity.

Medchemcomm 2019 Mar 14;10(3):390-398. Epub 2019 Jan 14.

Rega Institute for Medical Research , Department of Microbiology and Immunology , KU Leuven , 3000 Leuven , Belgium . Email:

Brazil has one of the largest biodiversities in the world. The search for new natural products extracted from the Brazilian flora may lead to the discovery of novel drugs with potential to treat infectious and other diseases. Here, we have investigated 9 lectins extracted and purified from the Northeastern Brazilian flora, from both leguminous species: (ConBr), (ConM), (DLasiL) and (DSclerL), and algae (AML), (BSL), (HML), (MEL) and (SfL). Read More

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http://dx.doi.org/10.1039/c8md00508gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430086PMC
March 2019
5 Reads

Discovery of small molecule inhibitors targeting the E3 ubiquitin ligase activity of the HSV-1 ICP0 protein using an high throughput screening assay.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

University of Kansas Medical Center, Department of Microbiology, Molecular Genetics, Immunology, 3901 Rainbow Blvd, Building Hixon, room 3009, Kansas City, KS, 66160

Herpes simplex virus-1 (HSV-1) has infected more than 80% of the population. Reactivation of the virus causes diseases ranging in severity from benign cold sores to fatal encephalitis. Current treatments involve viral DNA replication inhibitors but emergence of drug resistant mutants is observed frequently, highlighting the need for novel anti-viral therapies. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00619-19
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http://dx.doi.org/10.1128/JVI.00619-19DOI Listing
April 2019
3 Reads

Phosphoproteome analysis of cells infected with adapted and non-adapted influenza A virus reveals novel pro- and antiviral signaling networks.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus Liebig University, 35392 Giessen (Germany), Member of the German Center for Lung Research

Influenza A viruses (IAVs) quickly adapt to new environments and are well known to cross species barriers. To reveal a molecular basis for these phenomena, we compared the Ser/Thr and Tyr phosphoproteomes of murine lung epithelial cells early and late after infection with mouse-adapted SC35M virus or its non-adapted SC35 counterpart. With this analysis we identified a large set of upregulated Ser/Thr phosphorylations common to both viral genotypes, while Tyr phosphorylations showed little overlap. Read More

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http://dx.doi.org/10.1128/JVI.00528-19DOI Listing

An improved synthesis of adefovir and related analogues.

Beilstein J Org Chem 2019 29;15:801-810. Epub 2019 Mar 29.

School of Chemistry, University College Cork, Cork, Ireland.

An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium -butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. Read More

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https://www.beilstein-journals.org/bjoc/articles/15/77
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http://dx.doi.org/10.3762/bjoc.15.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444443PMC
March 2019
1 Read

Enterovirus 71 Suppresses miR-17-92 Cluster Through Up-Regulating Methylation of the miRNA Promoter.

Front Microbiol 2019 28;10:625. Epub 2019 Mar 28.

School of Life Sciences, Ningxia University, Yinchuan, China.

Enterovirus 71 (EV71), the etiological agent of hand-foot-and-mouth disease, has become an increasing public health challenge worldwide. Accumulating evidence suggests that mammalian microRNAs (miRNAs), a class of non-coding RNAs of 18 to 24 nucleotides (nt) with important regulatory roles in cellular processes, participate in host antiviral defense and studies have suggested roles of miRNAs in EV71 replication and pathogenesis. In the current study, we reported that the expression of hsa-miR-17∼92 cluster was significantly downregulated during EV71 infection. Read More

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https://www.frontiersin.org/article/10.3389/fmicb.2019.00625
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http://dx.doi.org/10.3389/fmicb.2019.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447709PMC
March 2019
2 Reads

Aryl and arylalkyl substituted 3-hydroxypyridin(1H)-2-ones: Synthesis and evaluation as inhibitors of influenza A endonuclease.

ChemMedChem 2019 Apr 14. Epub 2019 Apr 14.

Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, 08854-5627, U.S.A, UNITED STATES.

Seasonal influenza infections are associated with an estimated 250-500,000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A strains. Read More

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http://dx.doi.org/10.1002/cmdc.201900084DOI Listing

A clinical study for the evaluation of pharmacokinetic interaction between daclatasvir and fluoxetine.

J Pharm Biomed Anal 2019 Apr 5;171:104-110. Epub 2019 Apr 5.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71526, Egypt; Current address: Schulich School of Engineering, University of Calgary, Calgary, AB T2N 4V8, Canada. Electronic address:

A simple and sensitive chromatographic method has been developed for the quantitative analysis of an antiviral agent, daclatasvir (DCV), that commonly prescribed for the treatment of hepatitis C viral (HCV) infection. The method was applied to detect DCV in human plasma and real blood samples collected from patients diagnosed with HCV and treated with DCV. The analysis strategy was based on recording the native fluorescence of DCV in plasma, after pre-column treatment to precipitate the plasma proteins using a readily applicable protocol. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07317085183292
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http://dx.doi.org/10.1016/j.jpba.2019.03.065DOI Listing
April 2019
4 Reads

Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea

The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189947
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http://dx.doi.org/10.15252/embj.201899475DOI Listing
April 2019
1 Read

Marine Fungi from the Sponge : Biodiversity, Chemodiversity, and Biotechnological Potential.

Mar Drugs 2019 Apr 11;17(4). Epub 2019 Apr 11.

Mycotheca Universitatis Taurinensis, Department of Life Sciences and Systems Biology, University of Turin, Viale Mattioli 25, 10125 Turin, Italy.

The emergence of antibiotic resistance and viruses with high epidemic potential made unexplored marine environments an appealing target source for new metabolites. Marine fungi represent one of the most suitable sources for the discovery of new compounds. Thus, the aim of this work was (i) to isolate and identify fungi associated with the Atlantic sponge ; (ii) to study the fungal metabolites by applying the OSMAC approach (one strain; many compounds); (iii) to test fungal compounds for their antimicrobial activities. Read More

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https://www.mdpi.com/1660-3397/17/4/220
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http://dx.doi.org/10.3390/md17040220DOI Listing
April 2019
2 Reads

Determinants of Tenascin-C and HIV-1 envelope binding and neutralization.

Mucosal Immunol 2019 Apr 11. Epub 2019 Apr 11.

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.

Interactions between innate antiviral factors at mucosal surfaces and HIV-1 virions contribute to the natural inefficiency of HIV-1 transmission and are a platform to inform the development of vaccine and nonvaccine strategies to block mucosal HIV-1 transmission. Tenascin-C (TNC) is a large, hexameric extracellular matrix glycoprotein identified in breast milk and genital fluids that broadly neutralizes HIV-1 via interaction with the HIV-1 Envelope (Env) variable 3 (V3) loop. In this report, we characterize the specific determinants of the interaction between TNC and the HIV-1 Env. Read More

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http://dx.doi.org/10.1038/s41385-019-0164-2DOI Listing
April 2019
1 Read

Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses.

Antiviral Res 2019 Apr 7;167:25-34. Epub 2019 Apr 7.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, 53705-2222, USA. Electronic address:

Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01663542193001
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http://dx.doi.org/10.1016/j.antiviral.2019.04.004DOI Listing
April 2019
4 Reads

What are the effects of the serine triad on proton conduction of an influenza B M2 channel? An investigation by molecular dynamics simulations.

Phys Chem Chem Phys 2019 Apr 10. Epub 2019 Apr 10.

Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, Changchun 130023, People's Republic of China. and Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130023, People's Republic of China.

The tetrameric influenza B M2 channel (BM2), an acid activated proton channel, is important in the influenza virus B lifecycle. A conserved HxxxW motif is responsible for proton conduction and channel gating. In this study, to explore the effects of the serine triad (S9, S12 and S16) on proton conduction, we performed classical molecular dynamics (CMD) simulations and adaptive steered molecular dynamics (ASMD) simulations at different protonation states of the H19 tetrad. Read More

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http://xlink.rsc.org/?DOI=C9CP00612E
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http://dx.doi.org/10.1039/c9cp00612eDOI Listing
April 2019
4 Reads

Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a -1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNALeu that reads the UUA codon at the mRNA slippery site. Read More

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http://dx.doi.org/10.1093/nar/gkz202DOI Listing
April 2019
2 Reads

Halogen bond interactions of novel HIV-1 protease inhibitors (PI)(GRL-001-15 and GRL-003-15) with the flap of protease are critical for their potent activity against wild-type and multi-PI-resistant HIV-1 variants.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan

We newly generated two nonpeptidic HIV-1 protease inhibitors (PIs), GRL-001-15 and GRL-003-15, which contain a unique P2-crown-THF (THF) and P2'-cyclopropyl-amino-benzothiazole (Cp-Abt) moieties. GRL-001-15 and GRL-003-15 have --fluorophenyl and --fluorophenyl at the P1 site, exert highly potent activity against wild-type HIV-1 with 50% effective concentrations (ECs) of 57 and 50 pM, and have favorable cytotoxicity profiles with 50% cytotoxic concentrations (CCs) of 38 and 11 μM, respectively. The activity of GRL-001-15 against multi-PI-resistant HIV-1 variants was generally greater than that of GRL-003-15. Read More

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http://dx.doi.org/10.1128/AAC.02635-18DOI Listing
April 2019
1 Read

Conformational Dynamics of the HIV-Vif Protein Complex.

Biophys J 2019 Mar 23. Epub 2019 Mar 23.

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California. Electronic address:

Human immunodeficiency virus-1 viral infectivity factor (Vif) is an intrinsically disordered protein responsible for the ubiquitination of the APOBEC3 (A3) antiviral proteins. Vif folds when it binds Cullin-RING E3 ligase 5 and the transcription cofactor CBF-β. A five-protein complex containing the substrate receptor (Vif, CBF-β, Elongin-B, Elongin-C (VCBC)) and Cullin5 (CUL5) has a published crystal structure, but dynamics of this VCBC-CUL5 complex have not been characterized. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.03.014DOI Listing

Cell line-dependent activation and antiviral activity of T-1105, the non-fluorinated analogue of T-705 (favipiravir).

Antiviral Res 2019 Apr 2;167:1-5. Epub 2019 Apr 2.

KU Leuven, Rega Institute for Medical Research, Herestraat 49, B-3000 Leuven, Belgium. Electronic address:

The antiviral drug T-705 (favipiravir) and its non-fluorinated analogue T-1105 inhibit the polymerases of RNA viruses after being converted to their ribonucleoside triphosphate (RTP) metabolite. We here compared the activation efficiency of T-705 and T-1105 in four cell lines that are commonly used for their antiviral evaluation. In MDCK cells, the levels of T-705-RTP were markedly lower than those of T-1105-RTP, while the opposite was seen in A549, Vero and HEK293T cells. Read More

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http://dx.doi.org/10.1016/j.antiviral.2019.04.002DOI Listing

[Modeling and theoretical analysis of ring specific mimicry in view of isomerism within medicinal promising oligomers of "DIVEMA"].

Biomed Khim 2019 Feb;65(2):133-151

Topchiev Institute of Petrochemical Synthesis, RAS, Moscow, Russia; Research Center for Biomodulators, Health Research and Development Foundation, Moscow, Russia.

The furan or pyran related hetero cycles play basic role in structural units of nucleic acids (NA) and polysaccharides (PS), significantly predetermining their functional specifics. Some of such properties, in great relevancy for medicine, can be imitated through mimicry of polymers synthetic. Particularly, a formation of similar cycloisomeric chains is possible in process of free-radical cyclocopolymerization of divinyl ether (DVE) and maleic anhydride (MA). Read More

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http://dx.doi.org/10.18097/PBMC20196502133DOI Listing
February 2019
1 Read

Tick-borne flavivirus reproduction inhibitors based on isoxazole core linked with adamantane.

Bioorg Chem 2019 Mar 16;87:629-637. Epub 2019 Mar 16.

Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1 bd. 3, Moscow 119991, Russia; Institute of Physiologically Active Compounds, Severny Proezd 1, Chernogolovka, Moscow Region 142432, Russia. Electronic address:

Infections caused by flaviviruses pose a huge threat for public health all over the world. The search for therapeutically relevant compounds targeting tick-borne flaviviruses requires the exploration of novel chemotypes. In the present work a large series of novel polyfunctionalized isoxazole derivatives bearing substituents with various steric and electronic effects was obtained by our unique versatile synthetic procedure and their antiviral activity against tick-borne encephalitis, Omsk hemorrhagic fever, and Powassan viruses was studied in vitro. Read More

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http://dx.doi.org/10.1016/j.bioorg.2019.03.028DOI Listing
March 2019
4 Reads

A conceptual review of rhodanine: current applications of antiviral drugs, anticancer and antimicrobial activities.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1132-1148

a Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies , Shiraz University of Medical Sciences , Shiraz , Iran.

Rhodanines are accepted as advantaged heterocycles in medicinal chemistry as one of the 4-thiazolidinones subtypes. The aim of this paper is to analyze the features of rhodanine and its application in pharmacy and medicine. Some of the properties of rhodanine such as antiviral, anticancer, antimicrobial, and drug discovery have recently been reported. Read More

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http://dx.doi.org/10.1080/21691401.2019.1573824DOI Listing
December 2019
4 Reads

HLA-F*01:01-restricted peptides reveal to prefer a length of 16 amino acids with N-terminal flexibility.

Immunogenetics 2019 Apr 2. Epub 2019 Apr 2.

Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

HLA-F belongs to the non-classical HLA-Ib molecules with a marginal polymorphic nature and tissue-restricted distribution. HLA-F is a ligand of the NK cell receptor KIR3DS1, whose activation initiates an antiviral downstream immune response and lead to delayed disease progression of HIV-1. During the time course of HIV infection, the expression of HLA-F is upregulated while its interaction with KIR3DS1 is diminished. Read More

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http://dx.doi.org/10.1007/s00251-019-01112-1DOI Listing
April 2019
2 Reads

A survey of core replacements in indole-based HIV-1 attachment inhibitors.

Bioorg Med Chem Lett 2019 Mar 28. Epub 2019 Mar 28.

Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.

Indole- and azaindole-based glyoxylyl amide derivatives have been described as HIV-1 attachment inhibitors (AIs) that act by blocking the interaction between the viral gp120 coat protein and the human host cell CD4 receptor. As part of an effort to more deeply understand the role of the indole/azaindole heterocycle in the expression of antiviral activity, a survey of potential replacements was conducted using parallel synthesis methodology. The design and optimization was guided by a simple 2-dimensional overlay based on an overall planar topography between the indole/azaindole and C-7 substituents that had been deduced from structure-activity studies leading to the discovery of temsavir (3). Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.03.018DOI Listing
March 2019
2 Reads

Development and Validation of HPLC Fluorescence and UPLC/DAD Stability-Indicating Methods for Determination of Hepatitis C Antiviral Agent Daclatasvir.

J AOAC Int 2019 Apr 2. Epub 2019 Apr 2.

National Organization of Drug Control and Research (NODCAR), Giza, Egypt.

: Few stability-indicating chromatographic methods were published for determination of daclatasvir. All used UV detection. : This work aimed to develop rapid, specific, and novel stability-indicating methods using HPLC with fluorescence detection and ultra performance liquid chromatography (UPLC) with UV detection for the determination of daclatasvir in bulk powder and in its dosage form. Read More

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http://dx.doi.org/10.5740/jaoacint.18-0344DOI Listing
April 2019
1 Read

Nucleic Acids as a Nature-Inspired Scaffold for Macromolecular Prodrugs of Nucleoside Analogues.

Adv Sci (Weinh) 2019 Mar 28;6(6):1802095. Epub 2019 Jan 28.

Department of Chemistry and iNano Interdisciplinary Nanoscience Centre Aarhus University Aarhus C 8000 Denmark.

Macromolecular prodrugs (MP) built on the natural phosphodiester and deoxyribose backbone are developed using marketed antiviral nucleoside analogues. These MP are synthesized using automated synthesis, have defined molecular composition, and have a natural mechanism for drug release. These unique attributes, coupled to the efficient cell entry and potent antiviral effects, position the prodrugs scaffolded on nucleic acids favorably for translational studies. Read More

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http://dx.doi.org/10.1002/advs.201802095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425433PMC

TmToll-7 Plays a Crucial Role in Innate Immune Responses Against Gram-Negative Bacteria by Regulating 5 AMP Genes in .

Front Immunol 2019 12;10:310. Epub 2019 Mar 12.

Division of Plant Biotechnology, College of Agriculture and Life Sciences, Institute of Environmentally-Friendly Agriculture Chonnam National University, Gwangju, South Korea.

Although it is known that the Toll-7 receptor plays a critical role in antiviral autophagy, its function in other insects has not yet been reported. Here, we have identified a Toll-like receptor 7 gene, , in the coleopteran insect and examined its potential role in antibacterial and antifungal immunity. We showed that expression was significantly induced in larvae 6 h after infection with and and 9 h after infection with . Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2019.00310
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http://dx.doi.org/10.3389/fimmu.2019.00310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424196PMC
March 2019
1 Read

Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses.

Eur J Pharm Sci 2019 Mar 28;133:86-94. Epub 2019 Mar 28.

Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, United States. Electronic address:

Influenza virus infection causes substantial morbidity and mortality worldwide. The limited efficacy of oseltamivir in delayed treatment, coupled with the increasing incidences of oseltamivir-resistant strains, calls for next-generation of antiviral drugs. In this study, we discovered NMS-873, an allosteric and specific p97 inhibitor, as a broad-spectrum influenza antiviral through forward chemical genomics screening. Read More

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http://dx.doi.org/10.1016/j.ejps.2019.03.020DOI Listing

3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation.

Nucleosides Nucleotides Nucleic Acids 2019 Mar 31:1-14. Epub 2019 Mar 31.

a Applied Nucleic Acids Research Center , Zagazig University , Zagazig , Egypt.

Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. Read More

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http://dx.doi.org/10.1080/15257770.2019.1591445DOI Listing
March 2019
1 Read

Development and validation of a versatile HPLC-DAD method for simultaneous determination of the antiviral drugs daclatasvir, ledipasvir, sofosbuvir and ribavirin in presence of seven potential impurities. Application to assay of dosage forms and dissolution studies.

Drug Dev Ind Pharm 2019 Apr 1:1-9. Epub 2019 Apr 1.

c Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy , University of Alexandria , Alexandria , Egypt.

This study describes a simple, sensitive, specific and generic HPLC-DAD method for simultaneous determination of four drugs prescribed for treatment of Hepatitis C Virus (HCV) infection. Investigated drugs include daclatasvir (DAC), ledipasvir (LED), sofosbuvir (SOF) and ribavirin (RIB). Successful separation was accomplished using Thermohypersil BDS-C8 column (4. Read More

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http://dx.doi.org/10.1080/03639045.2019.1593444DOI Listing
April 2019
2 Reads

Complement C4 Prevents Viral Infection through Capsid Inactivation.

Cell Host Microbe 2019 Apr 26;25(4):617-629.e7. Epub 2019 Mar 26.

Protein and Nucleic Acid Chemistry Division, Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address:

The complement system is vital for anti-microbial defense. In the classical pathway, pathogen-bound antibody recruits the C1 complex (C1qC1rC1s) that initiates a cleavage cascade involving C2, C3, C4, and C5 and triggering microbial clearance. We demonstrate a C4-dependent antiviral mechanism that is independent of downstream complement components. Read More

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http://dx.doi.org/10.1016/j.chom.2019.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461443PMC
April 2019
1 Read

Anti-Zika Activity of a Library of Synthetic Carbohydrate Receptors.

J Med Chem 2019 Apr 8. Epub 2019 Apr 8.

Nanoscience Initiative, Advanced Science Research Center at the Graduate Center of the City University of New York , 85 St. Nicholas Terrace , New York , New York 10031 , United States.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders. Currently, there are no antiviral therapies that have been specifically approved to treat ZIKV, and there is an urgent need to develop effective anti-ZIKV agents. Here, we report anti-ZIKV activity of 16 synthetic carbohydrate receptors (SCRs) that inhibit ZIKV infection in Vero and HeLa cells. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.9b00142DOI Listing
April 2019
2 Reads

Stachyonic Acid: A Dengue Virus Inhibitor from Basilicum polystachyon.

Chemistry 2019 Apr 29;25(22):5664-5667. Epub 2019 Mar 29.

School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072, Queensland, Australia.

Stachyonic acid A, arising from the first in-depth phytochemical investigation of the herb Basilicum polystachyon, was found to display potent inhibitory activity against dengue virus, with limited cytotoxicity. Andrographolide, a known dengue virus inhibitor and closely related labdane-type diterpene, is structurally more complex but displayed poor antiviral activity in the PRNT assay, and increased cytotoxicity in comparison. Furthermore, a Diels-Alder reaction with PTAD identified the active pharmacophore of stachyonic acid to be the conjugated diene. Read More

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http://dx.doi.org/10.1002/chem.201900591DOI Listing
April 2019
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Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus.

PLoS One 2019 28;14(3):e0214646. Epub 2019 Mar 28.

Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.

Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214646PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438514PMC
March 2019
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Oxazole-benzenesulfonamide derivatives inhibit HIV-1 reverse transcriptase interaction with cellular eEF1A and reduce viral replication.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Qld, 4029, Australia

HIV-1 replication requires direct interaction between HIV-1 reverse transcriptase (RT) and cellular eukaryotic translation elongation factor 1A (eEF1A). Our previous work showed that disrupting this interaction inhibited HIV-1 uncoating, reverse transcription and replication, indicating its potential as an anti-HIV-1 target. Here we develop a sensitive, live-cell split luciferase complementation assay (NanoBiT) to quantitatively measure inhibition of HIV-1 RT interacting with eEF1A. Read More

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http://dx.doi.org/10.1128/JVI.00239-19DOI Listing
March 2019
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The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV.

Viruses 2019 Mar 26;11(3). Epub 2019 Mar 26.

Immunology Unit & Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

La Crosse virus (LACV) is a mosquito-transmitted arbovirus and the main cause of virus-mediated neurological diseases in children. To date, little is known about the role of C-type lectin receptors (CLRs)-an important class of pattern recognition receptors-in LACV recognition. DC-SIGN remains the only well-described CLR that recognizes LACV. Read More

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http://dx.doi.org/10.3390/v11030303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466035PMC
March 2019
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Structural bioinformatics insights into the CARD-CARD interaction mediated by the mitochondrial antiviral-signaling protein of black carp.

J Cell Biochem 2019 Mar 25. Epub 2019 Mar 25.

Biotechnology Laboratory, ICAR-Central Inland Fisheries Research Institute, Kolkata, West Bengal, India.

The innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral-signaling (MAVS) protein, are crucial for RLR-triggered interferon (IFN) antiviral immunity. Read More

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http://dx.doi.org/10.1002/jcb.28519DOI Listing

Compounds based on 5-(perylen-3-ylethynyl)uracil scaffold: High activity against tick-borne encephalitis virus and non-specific activity against enterovirus A.

Eur J Med Chem 2019 Jun 16;171:93-103. Epub 2019 Mar 16.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, Moscow 117997, Russia. Electronic address:

Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC values vary from 0. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02235234193024
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http://dx.doi.org/10.1016/j.ejmech.2019.03.029DOI Listing
June 2019
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Marine natural products as source of new drugs: a patent review (2015-2018).

Expert Opin Ther Pat 2019 Apr 3;29(4):283-309. Epub 2019 Apr 3.

a CSIR Unit for Research and Development of Information Products (CSIR-URDIP) , Pune , India.

Introduction: Natural products from plants, animals, microbes, and minerals have long been a traditional source for the treatment of human diseases. In the past decades, research on natural products for the pharmaceutical industry had declined due to numerous challenges. However, the recent developments in analytical technology, spectroscopy, and high-throughput screening have tremendously revived natural product drug discovery, including contribution from marine-based drugs. Read More

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http://dx.doi.org/10.1080/13543776.2019.1598972DOI Listing
April 2019
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Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus.

Molecules 2019 Mar 21;24(6). Epub 2019 Mar 21.

Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.

Tick-borne encephalitis virus (TBEV) is a causative agent of tick-borne encephalitis (TBE), one of the most important human infections involving the central nervous system. Although effective vaccines are available on the market, they are recommended only in endemic areas. Despite many attempts, there are still no specific antiviral therapies for TBEV treatment. Read More

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http://dx.doi.org/10.3390/molecules24061129DOI Listing
March 2019
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[A Plasmid-Expressed CRISPR/Cas9 System Suppresses Replication of HSV Type I in a Vero Cell Culture].

Mol Biol (Mosk) 2019 Jan-Feb;53(1):91-100

Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098 Russia.

Herpesviruses are widespread in the human population. Herpes simplex virus type 1 (HSV1) alone infects more than 3.7 billion people. Read More

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http://dx.doi.org/10.1134/S0026898419010051DOI Listing

Biological Significance of Imidazole-Based Analogues in New Drug Development.

Curr Drug Discov Technol 2019 Mar 20. Epub 2019 Mar 20.

Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut 250005. India.

In the field of heterocyclic medicinal chemistry, especially five membered ring structures containing nitrogen atom, imidazole core is an imperative aromatic heterocycle which is usually present in naturally occurring products and synthetic bioactive molecules. Occurrence of imidazole moiety in therapeutic compounds may be beneficial in terms of improving water soluble properties due to its two nitrogen atoms which leads to the creation of hydrogen bonds. The imidazole nucleus has also been recognized as an important isostere of triazole, pyrazole, thiazole, tetrazole, oxazole, amide etc. Read More

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http://dx.doi.org/10.2174/1570163816666190320123340DOI Listing

The inhibitory activities and antiviral mechanism of Viola philippica aqueous extracts against grouper iridovirus infection in vitro and in vivo.

J Fish Dis 2019 Mar 20. Epub 2019 Mar 20.

Guangxi Key Laboratory of Marine Environmental Science, Guangxi Academy of Sciences, Nanning, China.

Grouper iridovirus (GIV) is one of the most serious pathogens in mariculture and causes high mortality rates in cultured groupers; then, effective medicines for controlling GIV infections are urgently needed. Viola philippica is a well-known medicinal plant, and the application of V. philippica aqueous extracts against GIV infection was assessed by different methods in this study. Read More

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http://dx.doi.org/10.1111/jfd.12987DOI Listing
March 2019
2 Reads

Second Generation Inhibitors of HIV-1 Maturation.

ACS Med Chem Lett 2019 Mar 8;10(3):287-294. Epub 2019 Feb 8.

Department of Discovery Chemistry and Molecular Technologies Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, New Jersey 08543-4000, United States.

The strategy and tactics subtending the discovery and development of the second generation HIV-1 maturation inhibitor GSK-3532795/BMS-955176, a compound that exhibits a broader spectrum of antiviral effect in vitro and in clinical studies than the prototypical maturation inhibitor bevirimat, are described. Read More

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http://dx.doi.org/10.1021/acsmedchemlett.8b00656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421530PMC
March 2019
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[Association of baseline alanine aminotransferase levels with therapeutic effects of entecavir and interferon- in patients with chronic hepatitis B].

Nan Fang Yi Ke Da Xue Xue Bao 2019 02;39(2):150-155

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels.

Methods: We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)]. Read More

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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.09.04DOI Listing
February 2019
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Activity and structural analysis of GRL-117C: a novel small molecule CCR5 inhibitor active against R5-tropic HIV-1s.

Sci Rep 2019 Mar 18;9(1):4828. Epub 2019 Mar 18.

Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-1868, USA.

CCR5 is a member of the G-protein coupled receptor family that serves as an essential co-receptor for cellular entry of R5-tropic HIV-1, and is a validated target for therapeutics against HIV-1 infections. In the present study, we designed and synthesized a series of novel small CCR5 inhibitors and evaluated their antiviral activity. GRL-117C inhibited the replication of wild-type R5-HIV-1 with a sub-nanomolar IC value. Read More

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http://www.nature.com/articles/s41598-019-41080-w
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http://dx.doi.org/10.1038/s41598-019-41080-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423129PMC
March 2019
8 Reads

Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy.

Trends Mol Med 2019 Mar 15. Epub 2019 Mar 15.

Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

The advent of immunotherapy in recent years has shown the potential to revolutionize the treatment of cancer. Unleashing antitumor T cell responses via immune checkpoint blockade has led to remarkable responses in previously untreatable tumors. The master regulator of interferon-mediated antiviral responses - stimulator of interferon genes (STING) - has now emerged as a critical mediator of innate immune sensing of cancer, and is a promising target for local immunostimulation, promoting intratumoral inflammation, and facilitating antitumor T cell responses. Read More

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http://dx.doi.org/10.1016/j.molmed.2019.02.007DOI Listing
March 2019
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Study on the regioselectivity of the N-ethylation reaction of -benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide.

Beilstein J Org Chem 2019 12;15:388-400. Epub 2019 Feb 12.

Instituto de Química, Universidade Federal Fluminense, Niterói, 24020-150, Brazil.

4-Oxoquinolines are a class of organic substances of great importance in medicinal chemistry, due to their biological and synthetic versatility. -1-Alkylated-4-oxoquinoline derivatives have been associated with different pharmacological activities such as antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Read More

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http://dx.doi.org/10.3762/bjoc.15.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404479PMC
February 2019

Viperin interacts with the kinase IRAK1 and the E3 ubiquitin ligase TRAF6,  coupling innate immune signaling to antiviral ribonucleotide synthesis.

J Biol Chem 2019 Mar 14. Epub 2019 Mar 14.

University of Michigan, United States.

Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (viperin) is a radical SAM enzyme that plays a multifaceted role in the cellular antiviral response. Viperin has recently been shown to catalyze the SAM-dependent formation of 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), which inhibits some viral RNA polymerases. Viperin is also implicated in regulating Lys-63-linked polyubiquitination of interleukin-1 receptor-associated kinase-1 (IRAK1) by the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) as part of the Toll-like receptor-7 and 9 (TLR7/9) innate immune signaling pathways. Read More

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http://dx.doi.org/10.1074/jbc.RA119.007719DOI Listing

Potentials of Diphenyl Ether Scaffold as a Therapeutic Agent: A Review.

Mini Rev Med Chem 2019 Mar 12. Epub 2019 Mar 12.

Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, MAHE, Manipal, Karnataka. India.

Diphenyl ethers (DPE) and its analogs have exhibited an excellent potential for therapeutic and industrial applications. Since the 19th century, intensive research is perpetuating on the synthetic routes and biological properties of DPEs. Few well-known DPEs are Nimesulide, Fenclofenac, Triclosan, Sorafenib, MK-4965, and MK-1439 which have shown the potential of this moiety as a lead scaffold for different pharmacological properties. Read More

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http://www.eurekaselect.com/170657/article
Publisher Site
http://dx.doi.org/10.2174/1389557519666190312150132DOI Listing
March 2019
4 Reads