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KNOCKDOWN OF HOST ANTIOXIDANT DEFENSE GENES ENHANCES THE EFFECT OF GLUCANTIME ON INTRACELLULAR Leishmania braziliensis IN HUMAN MACROPHAGES.
Abstract Leishmaniasis is a neglected tropical disease affecting millions of people worldwide and represents a major public health problem. Information on protein expression patterns and functional roles within the context of Leishmania-infected human monocyte-derived macrophages (MDMs) under drug treatment conditions are essential to understand the role of these cells in leishmaniasis treatment. We analyzed functional changes in expression of human MDM genes and proteins during in vitro infection by Leishmania braziliensis and treatment with Glucantime (Sb(V)) using quantitative polymerase chain reaction (qPCR) a...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2017 Category: Microbiology Authors: Téllez J, Romero I, Soares MJ, Steindel M, Romanha AJ Tags: Antimicrob Agents Chemother Source Type: research

A Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene.
Abstract Human coronaviruses (HCoVs) cause 15-30% of mild upper respiratory tract infections. However, no specific antiviral drugs are available to prevent or treat HCoV infections to date. Here, we developed four infectious recombinant HCoVs-OC43 (rHCoVs-OC43), which express the Renilla luciferase (Rluc) reporter gene. Among these four rHCoVs-OC43, rOC43-ns2DelRluc (generated by replacing ns2 with the Rluc gene) showed robust luciferase activity with only a slight impact on its growth characteristics. Additionally, this recombinant virus remained stable for at least 10 passages in BHK-21 cells. The rOC43-ns2DelRl...
Source: Antimicrobial Agents and Chemotherapy - July 4, 2016 Category: Microbiology Authors: Shen L, Yang Y, Ye F, Liu G, Desforges M, Talbot PJ, Tan W Tags: Antimicrob Agents Chemother Source Type: research

Enhancement of the replication of HCV replicons of genotypes 1-4 by manipulation of CpG and UpA dinucleotide frequencies and use of cell lines expressing SECL14L2 - application for antiviral resistance testing.
Abstract Treatment for hepatitis C virus (HCV) has improved greatly through the use of direct acting antivirals (DAAs). However, their effectiveness and potential for drug resistance development in non-genotype 1 variants of HCV remains relatively unexplored as in vitro assays to assess drug susceptibility are poorly developed and unsuited for a transient transfection format. In the current study, we have evaluated effects of dinucleotide frequency changes in the replicon and the use of a SEC14L2-expressing cell line on the replication of HCV of different genotypes and evaluated the resulting assay formats for sus...
Source: Antimicrobial Agents and Chemotherapy - March 7, 2016 Category: Microbiology Authors: Witteveldt J, Martin-Gans M, Simmonds P Tags: Antimicrob Agents Chemother Source Type: research

Carboxymefloquine, the major metabolite of antimalarial drug mefloquine, induces drug metabolizing enzyme and transporter expression by activation of pregnane X receptor.
Abstract Malaria patients are frequently co-infected with HIV and mycobacteria causing tuberculosis, which increases the co-administration of drugs and thereby enhances the risk of pharmacokinetic drug-drug interactions. Activation of pregnane X receptor (PXR) by xenobiotics, including many drugs, induces drug metabolism and transport, thereby possibly resulting in attenuation or loss of the therapeutic response of drugs being co-administered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on non-artemisinin-type antimalarials are still missing. Therefore this study aims to...
Source: Antimicrobial Agents and Chemotherapy - October 13, 2014 Category: Microbiology Authors: Piedade R, Traub S, Bitter A, Nüssler AK, Gil JP, Schwab M, Burk O Tags: Antimicrob Agents Chemother Source Type: research

Targeted siRNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection.
This study describes a proof of concept study on the use of siRNA-immunoliposomes as a therapeutic agent against H5N1 influenza virus infection. SiRNA specific for influenza virus nucleoprotein (NP) mRNA was employed as the key antiviral agent to inhibit viral replication in this study. A humanized single-chain Fv antibody (huscFv) against the hemagglutinin (HA) of H5N1 highly pathogenic avian influenza (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells. The huscFv was decorated onto cationic PEGylated DC-Chol/DOPE liposomes to generate immunoliposo...
Source: Antimicrobial Agents and Chemotherapy - March 10, 2014 Category: Microbiology Authors: Khantasup K, Kopermsub P, Chaichoun K, Dharakul T Tags: Antimicrob Agents Chemother Source Type: research

Evaluation of Acanthamoeba myosin-IC as a potential therapeutic target.
Abstract Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by siRNA silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs were developed against the Acanthamoeba myosin-IC gene. Treated and control amoebae were cultured in growth and encystment medium in order to evaluate the induced effects after myosin-IC gene knock-down as we have anticipated that cyst formation may be impaired. The effective of silencing the myo...
Source: Antimicrobial Agents and Chemotherapy - January 27, 2014 Category: Microbiology Authors: Martín-Navarro CM, Lorenzo-Morales J, López-Arencibia A, Reyes-Batlle M, Piñero JE, Valladares B, Maciver SK Tags: Antimicrob Agents Chemother Source Type: research