ABSTRACT:Although a relatively large number of drugs that inhibit human immunodeficiency syndrome (HIV)-1 reverse transcriptase have been developed-such as AZT, d4T, ddI, 3TC, and ddC, which are chain terminating nucleoside analogs-resistance is still a major problem. Atomic charges, regioselective patterns of chemical reactivity, and other indices of biochemical activity may help us acquire a better understanding of how the drugs work and the mechanism of drug resistance. In this work, we investigated the above-mentioned nucleoside analogs using the ab initio Hartree-Fock method with 3-21G, 3-21G*, 6-31G, 6-31G*, 6-31G**, and 6-31ϩG** basis sets as well as B3LYP/6-31G**, including thus diffusion, polarization, and correlation effects to obtain fully optimized geometric parameters. Vibrational frequencies were calculated and we also investigated the effects of solvents, Mulliken, and natural bond orbital charge distribution, as well as hydrogen bond effects. We tried to correlate very low and very high anti-HIV activity with charges, vibrational stretching frequencies, interatomic distances, and the effect of solvents.

ABSTRACT:The presence of a heterocyclic ring containing a basic center linked via a methylene chain to a substituted guanidine or thiourea polar side chain, such as found in the H2-antagonist metiamide, which has an imidazole heterocyclic ring, has often been identified as one of the requirements for H2-antagonist activity. In ranitidine, on the other hand, the imidazole ring is substituted for a furan ring, yielding a more active biological H2 antagonist. In this work, we have used the ab initio Hartree-Fock (HF) and second-order Møller-Plesset (MP2) methods in order to investigate the open and folded ranitidine conformations, of the type observed in metiamide. Five basis sets (3-21G, 3-21+G * * , 6-31G, 6-31+G * * , and 6-31+G * * ) were used in order to obtain fully optimized geometric parameters that indicated good agreement with the experimental crystallographic data. We have also investigated in this work the effects of solvents in both ranitidine and metiamide. Monocationic ranitidine was also investigated. All our results, indicate that, as in metiamide, the folded conformation is also preferred. We have investigated Mulliken and natural bond order (NBO) charge distributions, electrostatic and hydrogen bond effects on stabilizing the conformations and discussed the interactions of ranitidine with the biological receptor.

BackgroundPreliminary studies showed the prevalence of a virus similar to human hepatitis B virus (HBV-like) in swine from farms in China and the molecular evidence of Hepadnavirus infection in domestic pigs herds in Brazil. In this study, we genetically characterize the swine Hepadnavirus strains in swine from slaughterhouses located in certified abattoirs from Rio de Janeiro State, Brazil and evaluate its hepatotropic potential.ResultsBile and liver samples from swine were positive for partial genome amplification (ORF S and ORF C), direct sequencing and viral load quantification. Sequencing of the gene encoding the surface antigen allowed classification of Hepadnavirus into genotypes, similar to HBV genotype classification. Indirect immunofluorescence confirmed the presence of HBsAg antigen in liver tissue sections.ConclusionsSo far our data suggest that commercial swine house an HBV-like virus and this relevant finding should be considered in studies on the origin and viral evolution.

A derivação fotoquímica é proposta como abordagem para induzir fluorescência intensa (412/465 nm) da eritromicina. Parâmetros experimentais importantes como o tempo de irradiação com UV e tipo e concentração de ácido usado para tratar a solução de analito foram ajustadas. Limites de detecção e quantificação de 0,025e 0,085 µg mL -1 foram obtidos com resposta linear até 200 µg mL -1 . O procedimento é seletivo em relação a antibióticos aminoglicosídicos (canamicina, gentamicina e amicacina). O método foi testado em formulações farmacêuticas e em uma vacina contendo eritromicina como conservante, com recuperações do analito entre 98 e 105%.Photochemical derivatization was proposed to enable intense fluorescence (412/465 nm) from erythromycin. Crucial experimental parameters such as type and concentration of the acid used to treat analyte solutions and UV irradiation time were adjusted. Limits of detection and quantification of 0.025 and 0.085 µg mL -1 were achieved with linear range up to 200 µg mL -1 . The procedure was selective towards the presence of aminoglycoside antibiotics (kanamycin, gentamycin and amikacin). The method was tested using pharmaceutical formulations and one vaccine composition containing erythromycin as a preservative component, with analyte recoveries between 98 and 105%.

With the recent outbreaks of Zika and Dengue virus infections in various countries worldwide, production of vaccines or diagnostic kits is an urgent public health demand. Production of a monoclonal antibody (mAb) that specifically binds to a common antigen shared by the Flavivirus genus will be necessary for new diagnostic kits or characterization and viral identity tests during vaccine development. This study aimed to cultivate, in serum-free conditions, the 4G2 hybridoma that produces an mAb, which recognizes a shared epitope from the Flavivirus genus. We compared 4G2 hybridoma growth and biochemical profiles between cells cultivated in batch mode over 10 days in roller bottles containing Dulbecco's modified Eagle's medium high glucose containing 10% fetal bovine serum medium or hybridomas directly adapted to Ex-Cell serum-free medium. Cellular parameters such as specific growth rate (μ), maximum cell concentration, specific l-lactate, and glucose and IgG rates were evaluated. Thereafter, we also compared total mAb volumetric productivity, purification yield, and mAb staining of Vero cells infected with Zika and Dengue-2 virus. Direct adaptation to serum-free conditions did not change hybridoma growth rate and mAb production under the conditions tested. Instead, serum-free mAb purification showed a higher yield with no alterations on mAb structure or mAb staining of Zika and Dengue Vero-infected cells.

Therapeutic strategies against systemic mycoses can involve antifungal resistance and significant toxicity. Thus, novel therapeutic approaches to fight fungal infections are urgent. Monoclonal antibodies (mAbs) are promising tools to fight systemic mycoses. In this study, mAbs of the IgM isotype were developed against chitin oligomers. Chitooligomers derive from chitin, an essential component of the fungal cell wall and a promising therapeutic target, as it is not synthesized by humans or animals. Surface plasmon resonance (SPR) assays and cell-binding tests showed that the mAbs recognizing chitooligomers have high affinity and specificity for the chitin derivatives. In vitro tests showed that the chitooligomer mAbs increased the fungicidal capacity of amphotericin B against Cryptococcus neoformans. The chitooligomer-binding mAbs interfered with two essential properties related to cryptococcal pathogenesis: biofilm formation and melanin production. In a murine model of C. neoformans infection, the combined administration of the chitooligomer-binding mAb and subinhibitory doses of amphotericin B promoted disease control. The data obtained in this study support the hypothesis that chitooligomer antibodies are of great potential as accessory tools in the control of cryptococcosis.

Introduction:The pandemic of SARS-CoV-2 brought interest to fabric industry to develop functional textiles formulated with antiviral and/or virucidal agents, able to inactivate virus and reduce risk of infection and transmission. The antiviral textiles could be use in production of individual protection equipment (IPE), but that fabrics need to be tested in many specific antiviral assays.Objective: This study aims to assess the antiviral efficacy of functional textiles using an antiviral activity evaluation platform, which uses as model viruses of respiratory transmission, such as Measles virus (Laboratory with Biosafety level 2 -NB-2) and/or SARS-CoV-2 virus (NB-3).Methodology: To meet this demand, it was designed a work plan, outlined a pricing strategy and developed a technical protocol adapted from ISO18184. Textile samples were analyzed at different steps: analysis of cytotoxicity in NB-2 and antiviral activity against the Measles virus (previous antiviral efficacy screening in NB-2) and/or against the SARS-CoV-2 virus in NB-3. Briefly, after cytotoxicity analysis approved, samples (20mm x 20mm) of control or formulated textiles were challenged with a virus suspension for 1 or 30 minutes (contact time/room temperature = Fabric plus Virus). Afterwards, washed out samples with recovered viruses were quantified by TCID50 method, using Vero CCL-81 cells to determine the virus infectivity titer. Likewise, antiviral samples submitted industrially washed were evaluated for wash-stable. The antiviral performance of products were measured and the differences among 2.0-3.0 (log TDID 50 /mL) or higher than 3.0 (log TDID50/mL) were considered as good or excellent effect, with antiviral efficacy higher than 99% or 99.9%, respectively.

Therapeutic strategies against systemic mycoses can involve antifungal resistance and significant toxicity. Thus, novel therapeutic approaches to fight fungal infections are urgent. Monoclonal antibodies (mAbs) are promising tools to fight systemic mycoses. In this study, mAbs of the IgM isotype were developed against chitin oligomers. Chitooligomers derive from chitin, an essential component of the fungal cell wall and a promising therapeutic target, as it is not synthesized by humans or animals. Surface plasmon resonance (SPR) assays and cell-binding tests showed that the mAbs recognizing chitooligomers have high affinity and specificity for the chitin derivatives. In vitro tests showed that the chitooligomer mAbs increased the fungicidal capacity of amphotericin B against Cryptococcus neoformans . The chitooligomer-binding mAbs interfered with two essential properties related to cryptococcal pathogenesis: biofilm formation and melanin production. In a murine model of C. neoformans infection, the combined administration of the chitooligomer-binding mAb and subinhibitory doses of amphotericin B promoted disease control. The data obtained in this study support the hypothesis that chitooligomer antibodies are of great potential as accessory tools in the control of cryptococcosis.