We have carried out the study of the photochemical properties of a series of synthetic meso-tetraphenylsulfonated porphyrins (TPPMS4) bonded to several metal ions such as: Cu(II), Zn(II), Pd(II), Mn(II), Fe(III), Ni(II) and Co(II) for the optimization of their clinical applications as antiviral agents against the human immunodeficiency virus (HIV-1) as well as the study of the in vitro antiviral photoinactivation mechanisms with future application in blood sterilization. A selective inhibition has been determined in the viral growth (HIV-1) when this is irradiated in the presence of the complex TPPFeS4 and TPPMnS4 (photosensitizer-mediated Type I reaction) as well as in the 1O2-mediated (Type II reaction) in the presence of TPPPdS4 and TPPZnS4, remaining cellular viability unaltered in each case.
The preexistence of mutations to integrase inhibitors in HIV-1-infected Venezuelan patients was evaluated. The integrase region of the HIV-1 genome was amplified by nested-PCR and sequenced in 57 isolates from both naive (n = 24) and treated patients who received protease and/or reverse transcriptase inhibitors (PI and RTI, n = 33), but were never exposed to integrase inhibitors. Only one primary integrase resistance mutation, not conferring drug resistance by itself, was found among these patients, although several minor viral mutations, equally distributed among naive and PI- and RTI-treated patients, were also found. In the limited number of samples, no relation was found among the presence of resistance mutations to PI or RTI and the presence of minor mutations to integrase. The absence of resistance to integrase inhibitors may be related to the recent introduction of these drugs in our country. The availability of in-house assays allows for a more comprehensive surveillance of drug resistance to integrase inhibitors in Venezuela.
The primary objective of this study was to search for natural products capable of inhibiting hepatitis B virus (HBV) replication. The research design, methods and procedures included testing hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest on the cell line HepG2 2.2.15, which constitutively produces HBV. The main outcomes and results were as follows: the species Euterpe precatoria, Jacaranda copaia, Jacaranda obtusifolia, Senna silvestris, Warscewiczia coccinea and Vochysia glaberrima exerted some degree of inhibition on HBV replication. The leaves of W. coccinea showed a significant antiviral activity: 80% inhibition with 100 µg mL⁻¹ of extract. This extract also exerted inhibition on covalently closed circular deoxyribonucleic acid (cccDNA) production and on HIV-1 replication in MT4 cells (more than 90% inhibition with 50 µg mL⁻¹ of extract). Initial fractionation using organic solvents of increasing polarity and water showed that the ethanol fraction was responsible for most of the antiviral inhibitory activities of both the viruses. It was concluded that Warscewiczia coccinea extract showed inhibition of HBV and HIV-1 replication. Bioassay-guided purification of this fraction may allow the isolation of an antiviral compound with inhibitory activity against both viruses.
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