Estudo do potencial antiviral sobre o Sars-Cov-2 dos compostos identificados no extrato bruto das folhas de Tetradenia riparia / Study of antiviral potential on Sars-Cov-2 of compounds identified in Tetradenia riparia leaves crude extract / Estudio del potencial antiviral sobre el Sars-Cov-2 de los componentes identificados en el extracto crudo de las hojas de Tetradenia riparia

A COVID-19 surgiu de forma repentina, acometendo milhões de pessoas e causando muitas mortes no mundo todo. Diante disso, torna-se necessário a busca de substâncias bioativas com propriedades antivirais. No Brasil, a espécie Tetradenia riparia foi inserida como planta ornamental exótica, com aroma intenso e agradável, sendo cultivada em parques, jardins, residenciais e hortos. O objetivo deste estudo foi identificar compostos presentes no extrato bruto das folhas de Tetradenia riparia com interesse antiviral. O extrato bruto das folhas secas foi obtido por maceração dinâmica por esgotamento do solvente e após, concentrado em evaporador rotativo. A composição química do extrato bruto foi analisada por cromatografia líquida de ultra eficiência acoplada à espectrometria de massas de alta resolução (UHPLC-ESI/qTOF). Foram identificados 31 compostos que foram investigados por meio de levantamento bibliográfico quanto ao seu potencial anti- SARS-CoV-2. Os compostos rosmanol, procianidina, cianidina, betulina, ácido betulínico e o ácido sagerínico, apresentaram potencial atividade antiviral sobre o SARS-CoV-2. Esta investigação é promissora, indicando possivelmente que no extrato bruto das folhas de T. ripária existem compostos que podem combater o SARS-CoV-2. Neste sentido, estudos de ancoramento molecular (docking) e análises in silico sobre a proteína Mpro do vírus devem ser realizadas corroborando desta forma a ação dos compostos identificados.

COVID-19 appeared suddenly, affecting millions of people and causing many deaths worldwide. Therefore, it is necessary to search for bioactive substances with antiviral properties. In Brazil, Tetradenia riparia was inserted as an exotic ornamental plant, with an intense and pleasant aroma, cultivated in parks, residential and vegetable gardens. This study aimed to identify compounds present in the crude extract of Tetradenia riparia leaves with antiviral interest. The crude extract of the dried leaves was obtained by dynamic maceration with solvent exhaustion and then concentrated in a rotary evaporator. The chemical composition of the crude extract was analyzed by ultra- performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC- ESI/qTOF). We identified 31 compounds investigated through a literature review for their anti- SARS-CoV-2 potential. The compounds rosmanol, procyanidin, cyanidin, betulin, betulinic acid, and sagerinic acid showed potential antiviral activity against SARS-CoV-2. Therefore, this investigation is promising, possibly indicating that in the crude extract of T. riparia leaves, there are compounds that can fight SARS-CoV-2. In this sense, molecular docking studies and in silico analyzes on the virus Mpro protein must be carried out, thus corroborating the action of the identified compounds.

SARS-CoV-19 ha aparecido repentinamente, afectando a millones de personas y causando muchas muertes en todo el mundo. Por ello, se hace necesaria la búsqueda de sustancias bioactivas con propiedades antivirales. En Brasil, la especie Tetradenia riparia ha sido introducida como planta ornamental exótica, con un aroma intenso y agradable, siendo cultivada en parques, jardines, residencias y centros de jardinería. El objetivo de este estudio fue identificar los compuestos presentes en el extracto crudo de las hojas de Tetradenia riparia con interés antiviral. El extracto crudo de las hojas secas se obtuvo por maceración dinámica por agotamiento del disolvente y después, se concentró en el evaporador rotatorio. La composición química del extracto crudo se analizó mediante cromatografía líquida de ultra rendimiento acoplada a espectrometría de masas de alto rendimiento (UHPLC-ESI/qTOF). Se identificaron 31 compuestos y se investigó su potencial anti-SARS-CoV-2 mediante un estudio bibliográfico. Los compuestos rosmanol, procianidina, cianidina, betulina, ácido betulínico y ácido sagerínico, mostraron una potencial actividad antiviral sobre el SARS-CoV-2. Esta investigación es prometedora, pues posiblemente indica que en el extracto crudo de las hojas de T. riparia hay compuestos que pueden combatir el SARS-CoV-2. En este sentido, deben realizarse estudios de docking y análisis in silico sobre la proteína Mpro del virus para corroborar la acción de los compuestos identificados.

Is Ozone therapy an adjunct treatment for SARS-CoV-2 / COVID-19 infection?

Abstract Up to today, there is no specific treatment against SARS-CoV-2 / COVID-19 infection; there the necessity to search for alternatives that help patients with COVID-19. The objective of this study was to review the use of ozone therapy as adjunct treatment for SARS-CoV-2 / COVID-19 infection, highlighting the mechanisms of action, forms of application and current clinical evidence. A systematic review was conducted in electronic databases, searching the terminology Ozone "or" Ozone therapy "and" SARS-CoV-2 or COVID-19 or Coronavirus. Results: nineteen studies were included; ten were editorials, comments, brief reports or reviews, and nine clinical studies. We found that ozone therapy could be favorable for treating patients infected with SARS-CoV-2 / COVID-19, through a direct antiviral effect, regulation of oxidative stress, immunomodulation and improvement of oxygen metabolism. Patients who were treated with ozone therapy responded favorably; therefore, ozone therapy appears to be a promising treatment for patients infected with SARS-CoV-2 / COVID-19. Its mechanism of action justifies its use as an adjuvant therapy; however, scientific evidence is based on case series and clinical trials are necessary to corroborate its effectiveness and safety.

Direct-acting antivirals for chronic Hepatitis C are effective and safe: an observational study in Londrina/PR

Abstract This study aimed to evaluate the effectiveness and safety of direct-acting antivirals in a Unified Health System pharmacy of Londrina, Brazil. A descriptive observational study was performed from June 2017 to June 2018. Sociodemographic, clinical, and therapeutic variables of patients were collected from secondary data sources. Effectiveness was evaluated by sustained virologic response (SVR) and safety was evaluated by adverse events (AEs) and drug interactions (DIs). The mean population (N=30) was 56.6±11.3 years old and almost all patients had comorbidities (93.3%) and concomitant drugs (96.7%). Effectiveness evaluation was possible in 17 patients, and all of them (100.0%) achieved SVR. Eighteen patients (60.0%) reported 38 AEs, mostly mild, such as stomach symptoms and headache. No statistical relation was found between AE occurrence and treatment duration, Ribavirin use, number of comorbidities or number of concomitant drugs. A total of 48 DIs were reported, 18 being severe, and were managed by the pharmacist. The study indicates that the treatment was effective and safe.

La acelerada búsqueda de candidatos terapéuticos contra SARS-CoV-2, métodos in silico: Revisión / The accelerated search for drug candidates against SARS-CoV-2, in silico methods: Review

El reposicionamiento de fármacos como la derivatización química, que se han aplicado en los estudios de descubrimiento y diseño de fármacos contra el SARS-CoV-2, dependen del ciclo de vida del virus, las dianas moleculares identificadas y un diseño basado en su estructura e interacciones moleculares. Se realizó una revisión extensa en las bases de datos públicas e institucionales RSCB-Protein Data Bank, ZINC, NCBI (PubMed, PMC), PubChem, Science Direct e instituciones como CDC, NIH y revistas científicas especializadas sobre los avances en la búsqueda de nuevas moléculas contra el nuevo coronavirus basadas en estudios in silico, detectándose más de 40,000 publicaciones sobre SARS-CoV-2 y cerca de 200 relacionadas a dichos estudios, las consideradas más relevantes fueron analizadas e incluidas en este artículo. Su análisis evidencia el avance acelerado de las herramientas computacionales y fortaleza del diseño de fármacos asistido por computadora (in silico approach) para la generación de nuevas moléculas con posibilidad de ser activas contra COVID-19 y presenta las principales dianas moleculares sobre la que actúan estos agentes con potencial antiviral.

The search of new applications for approved drugs by the regulatory authorities around the world, as well as their chemical derivatization in the search for new and effective drugs against SARS-CoV-2 depends of the viral life cycle, action of the drug and a receptor-based design. We performed a deep bibliographic research in peer reviewed scientific journals, data bases RSCB-Protein Data Bank, ZINC, NCBI (PubMed, PMC), PubChem, Science Direct and institutions (CDC, NIH) in the search of new molecules tested in silico against the novel coronavirus. As a result, we found more than 40,000 research papers related to SARS-CoV-2 and nearby 200 look on in silico studies, taking into consideration for this work all the more relevant for us, evidenced the accelerated advance and strength of the drug design assisted by computer (in silico approach) to develop new molecules that can be effective against COVID-19 and, at the same time, it exposes the main molecular targets.

Cytotoxicity and antiviral activity evaluation of Cymbopogon spp hydroethanolic extracts

Cymbopogon citratus and C. nardus are noteworthy among the several existing plant species displaying medicinal properties, due to the potential pharmacological activity of these species, including antiviral, antibacterial, antifungal and anti-trypanosomal activities. The objective of this study was to carry out in vitro toxicity tests of plant extracts from both species and analyze potential antiviral activity against Human mastadenovirus serotype 5 (HAdV-5). Two cell lines (A549 and VERO) were used and mitochondrial and lysosomal viability were determined by the MTT and neutral red assay, respectively, after two exposure times (24 hours and six days). The aim of these assays was to counteract the behavior of the extracts against the different cell lines and determine their non-toxic concentration range, in order to evaluate possible antiviral activity against HAdV-5. Plaque reduction and inhibition index of viral titer assays were performed using the maximum non-cytotoxic concentrations (MNCC) of each extract. The results indicate MNCC at 625 µg/mL for all extracts, except for Cymbopogon nardus obtained with 80% ethanol (CN80), which showed toxicity at concentrations higher than 312.5 µg/mL. CN80 was the only extract that displayed potential activity against HAdV-5, at a concentration of 75 µg/mL, becoming a candidate for extract fraction purification and/or the isolation of substances related to the observed antiviral activity

Prostaglandin A1 inhibits the replication of bovine viral diarrhea virus

ABSTRACT Bovine viral diarrhea virus can cause acute disease in livestock, leading to economic losses. We show that Prostaglandin A1 inhibits bovine viral diarrhea virus replication in Madin-Darby bovine kidney cells (94% inhibition using 5 µg/mL). Light and electron microscopy of infected cells shows that Prostaglandin A1 also prevents virus-induced vacuolization, but at higher concentrations (10 µg/mL).

Potencial antiviral da quercetina sobre o parvovírus canino / Antiviral potencial of quercetin in canine parvovirus

Avaliou-se o efeito do flavonoide quercetina na replicação do parvovírus canino in vitro por meio do ensaio de determinação da atividade virucida (ensaio 1), ensaio de determinação da atividade sobre a célula (ensaio 2) e ensaio de tempo de adição das drogas em diferentes etapas do ciclo replicativo viral (ensaio 3). A quercetina apresentou significante atividade antiviral, com valores máximos de redução do título viral de 96,3% no ensaio 1, 90% no ensaio 2 e 90% no ensaio 3. Os efeitos mais expressivos ocorreram nas etapas de adsorção e penetração viral. Os resultados deste trabalho sugerem a importância da quercetina para a medicina veterinária.

The in vitro effect of the flavonoid quercetin against canine parvovirus was evaluated. The antiviral activity of quercetin was evaluated by determining the virucidal activity (assay 1), determining the activity on the cell (assay 2) and using the time of addition assay to test the inhibition of the viral replication cycle (assay 3). Quercetin showed a significant antiviral activity, with maximum viral titer reduction of 96.3% in assay 1, 90% in assay 2 and 90% in assay 3. The most expressive effects occurred in the stages of viral adsorption and penetration. The results show the importance of quercetin for veterinary medicine.

Atividade antiviral de extratos de plantas medicinais disponíveis comercialmente frente aos herpesvírus suíno e bovino / Antiviral activity of commercially available medicinal plants on suid and bovine herpesviruses

O presente trabalho teve como objetivo pesquisar a atividade antiviral in vitro de plantas medicinais disponíveis comercialmente sobre herpesvírus suíno (SuHV-1) e bovino (BoHV-1). As espécies adquiridas foram Mikania glomerata, Cymbopogon citratus, Equisetum arvense, Peumus boldus, Solanum paniculatum, Malva sylvestris, Piper umbellatun e Solidago microglossa. A citotoxicidade dos extratos foi avaliada na linhagem celular MDBK pelas alterações morfológicas das células e obtenção da concentração máxima não citotóxica (CMNC) de cada planta. A atividade antiviral foi realizada com os extratos em suas respectivas CMNC e avaliada com base na redução do título viral e expressos em porcentagem de inibição. Os extratos aquosos de Peumus boldus e Solanum paniculatum apresentaram atividade antiviral sobre o SuHV-1 com 98% de inibição viral enquanto o de Peumus boldus inibiu apenas o BoHV-1 em 99%.

This paper aims to find commercially available medicinal plants showing antiviral activity in vitro on suid and bovine herpesviruses. The following species were tested: Mikania glomerata, Cymbopogon citratus, Equisetum arvense, Peumus boldus, Solanum paniculatum, Malva sylvestris, Piper umbellatun and Solidago microglossa. The cytotoxicity was evaluated by morphological changes in cells determining the maximum not cytotoxic concentration (MNCC). The antiviral activity was evaluated by viral title reduction. The extracts from Peumus boldus and Solanum paniculatum showed antiviral activity against SuHV-1 with 98% of inhibition. The extract of Peumus boldus also showed activity against BoHV-1 with 99% of inhibition.

Influência do estado nutricional de selênio sobre a progressão da infecção pelo HIV / Influence of selenium nutritional status on the progression of HIV infection

Infection by the human immunodeficiency virus (HIV) is a public health problem of global scale, the nutritional status of infected individual shaving a great influence on the progression of HIV infection. In this context, the mineral selenium seems to play an important role. Therefore, this study aimed to discuss the influence of selenium status on HIV infection progression from a literature review. It was found that, among many approaches, in vivo and in vitro studies showed that seleniummay cause changes in health status of HIV patients, as well as suppress virus replication, respectively. However, the results of several studies are contradictory. Thus, we conclude that it is extremely important to develop further studies aiming to elucidate the way in which the effects of selenium can be achieved by improving the diet therapy of patients with HIV.

La infección por el virus de la inmuno deficiencia humana (VIH) es un problema de salud pública de escala global, siendo que el estado nutricional de los individuos infectados por elvirus tiene gran influencia en el desarrollo de la enfermedad. En este contexto, el mineral selenio parece desempeñar un papel destacado. Por lotanto, este estudio tuvo por objetivo discutir la influencia del estado nutricional de selenio en el avance de la infección por el VIH por medio de una revisión de la literatura. Se encontró que, diversos estudios, "in vivo" e "in vitro" muestran que el micronutriente puede ejercer modificaciones en la salud de los portadores de VIH, bien como suprimir la replicación del virus, respectivamente. Pero, los resultados de los estudios muestran contradicciones. Portanto, es importante la realización de más investigación destinada a aclarar la influencia del selenio en la evolución de los pacientes con VIH, lo cual podría ayudar a mejorar el tratamiento dietoterápico de los portadores.

A infecção pelo vírus da imunodeficiência humana (HIV) é um problema de saúde pública de escala global, sendo que o estado nutricional dos indivíduos infectados pelo vírus exerce grande influência na progressão da infecção pelo HIV. Nesse contexto, o mineral selênio parece desempenhar papel de destaque. Com isso, este trabalho teve como objetivo discutir a influência do estado nutricional de selênio sobre a progressão da infecção pelo HIV a partir de revisão da literatura. Verificou-se que, entre muitas abordagens, estudos in vivo e in vitro mostraram que o micronutriente pode exercer modificações no estado de saúde de portadores do HIV, bem como suprimir a replicação do vírus, respectivamente. Porém, os resultados de vários trabalhos se mostram contraditórios. Assim, conclui-se que é de extrema necessidade a realização de mais estudos com o objetivo de elucidar a forma pela qual os efeitos do uso de selênio podem ser alcançados, aprimorando o tratamento dietoterápico dos pacientes portadores do HIV.

Desarrollo tecnológico de un antiviral de amplio espectro para administración parenteral: ribavirina 100 mg/mL / Technological development of a wide spectrum antiviral agent to parenteral administration: 100 mg/mL Ribavirin

Se describe el desarrollo de una formulación que contiene ribavirina como principio activo, a una concentración de 100 mg/mL que mantiene sus propiedades estables desde el punto de vista físico, químico y microbiológico. Se realizaron los estudios de formulación correspondientes con el objetivo de determinar la formulación idónea, el procedimiento tecnológico y el envase adecuado para garantizar la estabilidad del producto terminado. Se elaboraron 3 lotes del medicamento, los cuales se envasaron en bulbos incoloros de vidrio, con calidad hidrolítica I y se almacenaron a temperatura ambiente de 30 ± 2 ºC durante 12 meses; se estudió su estabilidad física y química por el método acelerado y de vida de estante. Se comprobó su estabilidad microbiológica a través de un ensayo de esterilidad, a cada uno de los lotes elaborados, al inicio y final del estudio, según la Farmacopea de los Estados Unidos 30 y la regulación establecida por el Centro Estatal de Control de Medicamentos de Cuba; se obtuvieron resultados satisfactorios. Se realizó un estudio toxicológico del inyectable que mostró un amplio margen de seguridad para ser usado en humanos. Todos los resultados obtenidos cumplieron con los límites de calidad establecidos en la literatura oficial para este tipo de forma farmacéutica, por lo que se llegó a la conclusión que el medicamento desarrollado está correctamente formulado desde el punto de vista galénico con un tiempo de vida útil de 12 meses, almacenado bajo las condiciones estudiadas. Finalmente el medicamento fue introducido al nivel industrial sin que se presentaran problemas tecnológicos

Development of a formula containing Ribavirin as active principle at a 100 mg/mL concentration maintaining its stable properties from the physical, chemical and microbiological point of view is described. The aim of present formula studies was to determine the suitable formula, the technological procedure and the appropriate package to guarantee stability of end product. Three drugs batches were manufactured, which were packing in colourless glass bulbs with a hydrolytic I quality and stored at room temperature of 30 ± 2 ºC for 12 months; its physical and chemical was studied by accelerated method and shelf life. Its microbiological stability was verified by sterility trial in each of processed batches at study onset and at the end according to USA Pharmacopeia-30 and the regulation established by Cuban State Center for Drug Control with satisfactory results. A toxicology study was conducted of injectable agent showing a wide safety margin to human use. All results obtained fulfilled the quality limits established in official literature for this type of pharmaceutical way thus concluded that the developed drug is properly formulated from the medical point of view with a useful life time of 12 months, stored under study conditions. Finally, the drug was introduced at industrial level without technological problems

Ribunucleasas: su potencial terapeutico en infecciones virales / Ribonucleases: Theurapetical potential on Viral Infections

En la actualidad existe un gran interés por identificar proteínas o péptidos antimicrobianos que puedan ser herramientas terapéuticas que eviten el establecimiento o permitan el control de diferentes infecciones. Las ribonucleasas (RNasas), pertenecientes a la superfamilia Ribonucleasa A, son enzimas que participan en varios procesos fisiológicos, que van desde el procesamiento alternativo del RNA hasta la angiogénesis. Estas enzimas son expresadas por diferentes tejidos y exhiben especificidades variables contra diferentes sustratos de RNA. El potencial terapéutico de las RNasas se ha sugerido en procesos oncogénicos; adicionalmente, se ha descrito que tienen actividad antiviral directa y el potencial de activar células del sistema inmune innato induciendo su maduración y la producción de citoquinas proinflamatorias. Nuestro grupo de investigación ha realizado estudios que señalan la capacidad de cuatro RNasas recombinantes: EDN, 4EDN, RNasa A y angiogenina de inhibir la replicación del virus de la inmunodeficiencia humana tipo 1 en linfocitos T de sangre periférica activados. En este artículo se revisará la clasificación de las ribonucleasas que constituyen la superfamilia RNasa A y se describirá, en forma detallada, lo que se conoce de la función biológica, acción antiviral y mecanismo de acción de las RNasas a las que se les ha reportado actividad antiviral.

Antivirais / Antivirals

Doenças causadas por vírus representam dificuldades terapêuticas. O conjunto de medicamentos antivirais disponíveis é ainda relativamente pequeno, mas tem crescido nos últimos anos em razäo de enormes investimentos materiais e de talentos: a síndrome da imunodeficiência adquirida é, certamente, o motivo principal dessa procura, mas näo o único. Com a presente atualizaçäo, dedicada a oftalmologistas, o modo de açäo, as aplicaçöes, os efeitos adversos, as apresentaçöes e a posologia dos principais quimioterápicos desse grupo, assim como novidades e perspectivas, säo aqui resumidas

Some biological properties of the human amniotic membrane interferon

Human amniotic interferon was investigated to define the species specificity of its antiviral action and compare its anti-cellular and NK cell stimulating activities with those of other human interferons. The antiviral effect was titrated in bovine (RV-IAL) and monkey (VERO) cells. Amniotic interferon exhibited, in bovine cells, 5% of the activity seen in monkey cells, while alpha interferon displayed 200%. No effect was detected with either beta or gamma interferon in bovine cells. Daudi cells were exposed to different concentrations of various interferons and the cell numbers were determined. The anticellular effect of the amniotic interferon reached its peak on the third day of incubation. Results suggested a higher activity for alpha and gamma interferons and a lower activity for beta when compared to amniotic interferon. Using total mononuclear cells as effector cells and K 562 as target cell in a 51Cr release assay, it was demonstrated that low concentrations of amniotic interferon consistently stimulated NK cell activity in cells derived from several donors, the results indicating a higher level of activity with this interferon than with alpha and beta interferons

Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus.

Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing.