CONICET | Buscador de Institutos y Recursos Humanos

The emergence of antiviral drug-resistant mutants is the most important issue in current antiviral therapy. An ideal therapeutic target to prevent drug-resistance development is represented by host factors that are crucial for the viral life cycle. Given that viruses are obligate parasites, several host factors that are crucial for viral replication also represent antiviral therapeutic targets, referred to as the ?cell-based approach?.Viral hemorrhagic fevers (HF) are zoonoses able to cause dramatic and devastating local outbreaks in man. The ethiological agents are four very different types of RNA viruses classified in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. These viruses can often produce a subclinical infection or a mild febrile syndrome, but the more severe forms of hemorrhagic disease are associated with extremely high morbidity and mortality. Despite of this threat for human health and although different types of compounds were evaluated for HF inhibition, no specific and safe chemotherapy for any viral HF is currently available for clinical use. Recent efforts have focused on finding and characterizing cellular metabolic inhibitors as broad-spectrum antivirals for targeting with minimum cytotoxicity. MPA is a non-nucleoside, non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH). It is well known by its effects as immunosuppressive and against multiplication of several viruses; this inhibition was highly reversed by exogenous guanosine addition, indicating that antiviral activity is effectively associated with GTP depletion through IMPDH blockade.Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as DENV, ZIKV, HIV, Hepatitis. Despite the high efficiency of the human immune system, viruses are ubiquitous and versatile organisms with the potential to cause serious illnesses that require aggressive pharmacological intervention, yet existing medicines are by and large inefficient at combatting viruses, making them a target for aggressive exploration to accelerate the development of new antiviral agents. In order to solve those problems, sustained drug release systems by using nano-particles or micro-particles are required. As it is known nanocarriers can provide key advantages for the in vivo delivery of drugs or molecules with therapeutic effects, such as nucleic acids and proteins, improving their efficiency and reducing potential side and toxic effects. Biodegradable and biocompatible nanoparticles (NPs) offer the ability to protect the therapeutic molecule from early degradation (i.e. before reaching the target organ or tissue), to control the release, to bypass the biological barriers and to selectively reach the action site. Despite nanobiotechnology, nanocarriers and NPs have had considerable development in recent years, especially in the field of biomedicine and electronics.Our results show, the binding interaction between MPA and BSA was confirmed by fluorescence spectroscopy and dissociation constants of Kd = 12,0 µM ± 0,7 µM in PBS and Kd = 4,7 µM ± 1,0 µM in water were estimated. The docking analyzes for MPA and BSA three of the six conformations with greatest predicted affinity, mycophenolate probably interacts with the BSA in the same manner as naproxen. In particular, for the three different binding modes, the main interactions of the carboxylate end and the aromatic fused rings are completely conserved. Circular dichroism (CD) spectroscopy. The far-UV CD spectra shows the prevalently α-hélix structure of BSA and a subtle decrease in its characteristic signal with higher concentrations of MPA. We obtained nanoparticles of approximately 10 and 100 -200 nm respectively, as shown by Scanning Electron Microscopy and Dynamic Light Scattering particle analysis. The particles were evaluated for their cytotoxic effect in vitro that proved to be non-toxic, according to the MTT and violet crystal method using standard concentrations. The nanoparticles with MPA were not better than MPA free in promoting the antiviral effect. We will give more antiviral effect using another synthesis method to obtain nanoparticles and in that way improving antiviral drugs effect