The omnipresent power of the invisible: From viruses to being conscious

According to Mayan cosmology, the law of time is represented as the energy factored by time equals to art. Time is a form of biological information. Time in-forms life, in such a way that life forms processes time as information and externalize it specific forms into the three-dimensional world, then time is the principle ordering of life. Indeed, everything in the natural order of the cosmos is beauty and harmony. All life forms on planet earth have their phases of morphological development, this is real even in the social structure of communities of living beings that also may have an aesthetic or artistic quality. This form and measurements of all things constitutes the entire or holistic order of the universe. So, if life is it nothing more than better-informed matter, where does this information come from? Socrates and Platon held that nothing in nature and in the world can be explained by random or chance, as Democritus would have argued, that nature creations occur because they have a Purpose. According to Platon, the natural world is a designer?s result demiurge or a universal consciousness that sets everything in the best possible place. So, if there is a start point where intelligence creates order, where there is order, there is purpose so; what is the purpose then? This work tends to give an answer and show a different perspective of living, studying and understanding (micro)biological phenomena in order to become conscious and assume that Nature is infinitely more powerful than us, the Whole is more than the sum of parts, we are part of it.Fil: Castañeda Cataña, Mayra Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

In Times of Global Planetary Challenges: Metanoia

We grow up in a perspective of an existence, which we call reality. We identify our-selves with this reality as something absolute and we reject the experiences that do not belong to it. Each reality is valid only within certain limits (such as family’s traditions, religious beliefs, culture etc). So, “this is how our own state of consciousness perceives reality and we can never explore reality without exploring ourselves the reality that we explore” reminds us of Ram Dass. Therefore, the numerous crises that arise in our time, ecological, humanitarian, economic, religious, political, show us how we perceive our-selves: mostly as indifferent and without being aware of nature. This work leads us to deeply think about the fact, that as we are living in the Anthropocene era we can prac-tice a different committed science that helps us clarify and manifest proposals, that will help us to deal with this planetary crisis, from new perspectives or metanoia (from Greek μετανοιεν, metanoien a change of mind or direction, new mind).Fil: Castañeda Cataña, Mayra Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein

The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.Fil: Linero, Florencia Natalia. Flanders Interuniversity Institute For Biotechnology; Bélgica. University of Ghent; BélgicaFil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Christopoulou, Ioanna. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Hulpiau, Paco. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Saelens, Xavier. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgic

Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity.

Several arenaviruses can cause severe hemorrhagic fever (HF) in humans, representing a public health threat in endemic areas of Africa and South America. The present study characterizes the potent virucidal activity of the carboxamide-derivatized aromatic disulfide NSC4492, an antiretroviral zinc finger-reactive compound, against Junín virus (JUNV), the causative agent of Argentine HF. The compound was able to inactivate JUNV in a time and temperature-dependent manner, producing more than 99 % reduction in virus titer upon incubation with virions at 37 °C for 90 min. The ability of NSC4492-treated JUNV to go through different steps of the multiplication cycle was then evaluated. Inactivated virions were able to bind and enter into the host cell with similar efficiency as control infectious particles. In contrast, treatment with NSC4492 impaired the capacity of JUNV to drive viral RNA synthesis, as measured by quantitative RT-PCR, and blocked viral protein expression, as determined by indirect immunofluorescence. These results suggest that the disulfide NSC4492 targets on the arenavirus replication complex leading to impairment in viral RNA synthesis. Additionally, analysis of VLP produced in NSC4492-treated cells expressing JUNV matrix Z protein revealed that the compound may interact with Z resulting in an altered aggregation behavior of this protein, but without affecting its intrinsic self-budding properties. The potential perspectives of NSC4492 as an inactivating vaccinal compound for pathogenic arenaviruses are discussed.Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica;Fil: Garcia, Cybele. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica;Fil: Levingston Mac Leod, Jesica Mariana. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Cs. y Tecnologia "dr. Cesar Milstein";Fil: Lopez, Nora Mabel. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Cs. y Tecnologia "dr. Cesar Milstein";Fil: Damonte, Elsa Beatriz. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica

Development of a Reverse Genetic System to Generate Recombinant Chimeric Tacaribe Virus that Expresses Junín Virus Glycoproteins

Mammarenaviruses are enveloped and segmented negative-stranded RNA viruses that comprise several pathogenic members associated with severe human hemorrhagic fevers. Tacaribe virus (TCRV) is the prototype for the New World group of mammarenaviruses and is not only naturally attenuated but also phylogenetically and antigenically related to all South American pathogenic mammarenaviruses, particularly the Junín virus (JUNV), which is the etiological agent of Argentinian hemorrhagic fever (AHF). Moreover, since TCRV protects guinea pigs and non-human primates from lethal challenges with pathogenic strains of JUNV, it has already been considered as a potential live-attenuated virus vaccine candidate against AHF. Here, we report the development of a reverse genetic system that relies on T7 polymerase-driven intracellular expression of the complementary copy (antigenome) of both viral S and L RNA segments. Using this approach, we successfully recovered recombinant TCRV (rTCRV) that displayed growth properties resembling those of authentic TCRV. We also generated a chimeric recombinant TCRV expressing the JUNV glycoproteins, which propagated similarly to wild-type rTCRV. Moreover, a controlled modification within the S RNA 5′ non-coding terminal sequence diminished rTCRV propagation in a cell-type dependent manner, giving rise to new perspectives where the incorporation of additional attenuation markers could contribute to develop safe rTCRV-based vaccines against pathogenic mammarenaviruses.Fil: Foscaldi, Sabrina Andrea. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Loureiro, Maria Eugenia. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Palacios, Carlos Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Forlenza, María Belén. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Lopez, Nora Mabel. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; Argentin

Antiviral activity against Zika virus of a new formulation of curcumin in poly lactic-co-glycolic acid nanoparticles

Objectives: In the search of an effective antiviral formulation, the natural product curcumin (CUR) was encapsulated into poly(lactic-co-glycolic acid) nanoparticles, a non-toxic bioresorbable and biocompatible copolymer. The resulting CUR containing particles (PLGA-CUR NPs) were characterized and analysed for antiviral activity against Zika virus (ZIKV) infection. Methods: The PLGA-CUR NPs were characterized by Fourier transform infrared, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy and thermogravimetric analysis and release profile. Cytotoxicity of PLGA-CUR and the antiviral activity against ZIKV were determined in Vero cells. The effect of PLGA-CUR NPs on viral RNA synthesis and protein expression was analysed by RT-qPCR and immunofluorescence staining, respectively. Key findings: The PLGA-CUR NPs showed an appropriate in vitro drug release profile. Our studies of the antiviral activity of PLGA-CUR NPs and CUR against ZIKV by virus yield reduction as well as viral RNA synthesis and protein expression have shown that PLGA-CUR formulation is more effective than free CUR to inhibit ZIKV infection of Vero cells. Conclusions: Our results demonstrate for the first time the antiviral activity against ZIKV of PLGA nanoparticles charged with CUR, suggesting that PLGA-CUR NPs are promising candidates for a drug formulation against human pathogenic flaviviruses.Fil: Pacho, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Pugni, Eugenio Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Diaz Sierra, Johanna Briyith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Morell, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentin

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Antiviral strategies for the prevention and treatment of infections with arenavirus: inhibitory activity of disulfides and acridones against junin virus

En el presente trabajo se realizó la evaluación de la actividad biológica de diversos compuestos que incluyeron disulfuros aromáticos, disulfuros de tiuramo, tiosulfonas y acridonas, encontrándose compuestos con una muy selectiva actividad antiviral y potente efecto virucida contra varios miembros de la familia Arenaviridae. El disulfuro aromático NSC4492 mostró el efecto virucida más potente, y los más efectivos agentes antivirales resultaron el disulfuro de tiuramo NSC14560 y la acridona 3f, las tiosulfonas fueron totalmente inactivas. Los compuestos antivirales NSC14560 y 3f resultaron igualmente efectivos en distintos tipos celulares. Estudios mecanísticos de la actividad antiviral indicaron que la acción de estos compuestos parecería afectar pasos tempranos e intermedios de la infección viral, sin bloquear la entrada del virus a la célula. La síntesis del RNA viral se vio inhibida con ambos compuestos, y, para el caso de 3f, fue posible recuperar parcialmente la infectividad y los niveles de RNA por el agregado de guanosina exógena. Los compuestos inactivantes mostraron ser efectivos también contra varios arenavirus, con una cinética de inactivación rápida y dependiente de la temperatura. El tratamiento con NSC4492 no mostró efectos sobre el autoensamblaje y la brotación de partículas tipo virales (VLPs) pero sí una alteración en el patrón electroforético de la proteína Z y una fuerte inhibición en la síntesis del RNA viral. En conclusión, se han detectado nuevos compuestos con potente y selectiva acción antiviral contra los arenavirus que parecen interferir con procesos relacionados a la síntesis de RNA viral así como agentes con fuerte capacidad inactivante de los viriones que alteran irreversiblemente proteínas virales de JUN lo que conduciría a la pérdida de la infectividad viral.In the present study we evaluated the biological activity of various compounds including aromatic disulfides, thiuram disulfide, thiosulfones and acridones finding compounds with highly selective antiviral activity and potent virucidal effect against several members of the family Arenaviridae. The aromatic disulfide NSC4492 showed the most potent virucidal effect, and the most effective antiviral agents were thiuram disulfide NSC14560 and acridone 3f, the thiosulfones were totally inactive. Antiviral compounds NSC14560 and 3f were equally effective in different cell types. Mechanistic studies of antiviral activity indicated that these compounds affect early and intermediate steps of viral infection, without blocking viral entry into cells. Viral RNA synthesis was inhibited with both compounds and, in the case of 3f, it was possible to partially restore the infectivity and RNA levels by adding of exogenous guanosine. Inactivating compounds shown to be effective also against several arenavirus, with fast inactivation kinetics and temperature dependent. NSC4492 treatment showed no effect on the self-assembly and budding of virus-like particles (VLPs) but an alteration in the electrophoretic pattern of protein Z and a strong inhibition of viral RNA synthesis were evidenced. In conclusion, we have identified new compounds with potent and selective antiviral action against arenavirus that seem to interfere with processes related to the synthesis of viral RNA as well as inactivating agents with strong capacity of virions that alter JUNV viral proteins and lead to the loss of viral infectivity.Fil:Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina