Author Correction: In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2.

The original version of the acknowledgement unfortunately contained a mistake.

In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2.

BACKGROUND: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. METHODS: To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. RESULTS: In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 µg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 µg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50µg/ml Echinaforce®. CONCLUSIONS: These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.

Da sala de aula à práxis clínica no contexto do Sistema Único de Saúde: o currículo de Farmácia frente às necessidades da população brasileira / From the classroom to the clinical practice within the National Healtcare System: Pharmacy's curriculum facing Brazilian population's needs

As mudanças ocorridas no Sistema Único de Saúde nos últimos anos, associadas às mudanças nas políticas educacionais, forçaram uma modificação na atuação do profissional farmacêutico. Nesse sentido, o farmacêutico necessita adquirir capacitação para atuar em conjunto com a Equipe Multiprofissional de Saúde. O objetivo deste trabalho foi avaliar se o ensino superior em Farmácia no Brasil capacita o farmacêutico a atuar em colaboração com a Equipe Multiprofissional de Saúde dentro dos preceitos do Sistema Único de Saúde. Com base em metodologia quanti-qualitativa, este trabalho analisou projetos político-pedagógicos e o cenário clínico de hospitais universitários de cinco instituições de ensino superior brasileiras, e estudou, a partir de questionários qualitativos, aplicados a diversos profissionais de saúde, as necessidades da equipe em relação à atividade do farmacêutico. Verificou-se inserção ainda modesta do farmacêutico, muitas vezes causada pela falta de conhecimento da equipe sobre sua função ou por uma sensação de falta de preparo do próprio profissional. Também, a análise dos documentos oriundos dos cursos permitiu a constatação da falta de um olhar direcionado para o Sistema Único de Saúde e para a formação clínica. Poucas iniciativas curriculares tem surgido nesse sentido. Por fim, são apresentadas propostas, por meio de mapeamento conceitual, para se pensar um currículo em que coexistam a formação técnica, já tradicional, e a formação clínica, permitindo abarcar essa última, deixada de lado a partir de meados do século XX, que retorna hoje como uma demanda social

Recent modification in the Brazilian's Public Health System, associated with changes in educational policies for higher education, forced a change in the pharmacist's professional performance area. Accordingly, the pharmacist needs to acquire capacity to act in conjunction with the Health Multidisciplinary Team. The objective of this thesis was to evaluate whether higher education in Brazil Pharmacy Schools enables the professional to work in collaboration with the Health Multidisciplinary Team within the precepts of National Public Health System. Based on quantitative and qualitative methodology, this study analyzed political-pedagogical projects and the clinical setting of university hospitals of five Brazilian higher education institutions, and studied from qualitative questionnaires applied to various health professionals the needs of the Multidisciplinary Health Team in having as a team member the pharmacist. There was verified a still modest insertion of the pharmacist in health teams, often caused by lack of staff knowledge about their function or by a sense of lack of readiness of the professional himself. Also, the analysis of documents from Pharmacy courses led to confirmation of the lack of educational policies directed to the National Public Health System and clinical training. Few curriculum initiatives have arisen in this regard. Finally, proposals are developed through conceptual mapping, to think of a Pharmacy course curriculum that can coexist in both the technical training as clinical training, allowing embrace this professional area of actuation that was set aside from the mid-twentieth century and returns today as a social demand

Antiulcerogenic potential activity of free and nanoencapsulated Passiflora serratodigitata L. extracts.

This paper provides evidence that the leaves and stem of Passiflora serratodigitata L. dry crude extract (DCE), ethylacetate fraction (EAF), and residual water fraction show potential antiulcerogenic activity. Interestingly, the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug delivery systems and allowed overcoming challenges such as poor aqueous solubility as well as the physical-chemical instability of the organic extract, which presented 90% (w/w) of the flavonoid content. The entrapment efficiency of the total flavonoid was 90.6 ± 2.5% (w/v) for the DCE and 79.9 ± 2.7% (w/v) for the EAF. This study shows that nanoencapsulation improves both the physicochemical properties and the efficacy of the herbal formulations. Therefore, free and encapsulated extracts have the potential to be suitable drug design candidates for the therapeutic management of ulcer.

Passiflora alata Curtis: a Brazilian medicinal plant: [review] / Passiflora alata Curtis: una planta medicinal brasileña: [revisión]

This review describes botanical, chemical, pharmacological and phytotechnological properties of Passiflora alata Curtis, with emphasis on analytical methods. Native to Brazil, P. alata is featured in several pharmaceutical preparations registered by the regulatory agency ANVISA. In four of the five editions of the Brazilian Pharmacopoeia, P. alata leaves have been included under the designation of “maracujᔠor “maracujá doce” (sweet passion fruit). This species is cited as Passiflora alata Curtis and was originally published in 1788 in the Botanical Magazine. In the last decade, phytochemical and pharmacological studies of Brazilian researchers related to this plant have increased. Despite several studies, the substances responsible for the anxiolytic, sedative, antioxidative and antiulcer activities attributed to passifloras remain unknown. Analytical methods for the quantification of markers are being developed in order to improve quality control analysis and to better understand the relationship between chemical markers and their pharmacological effects. Those methods include spectrophotometry, high performance thin-layer chromatography (HPTLC) and high performance liquid chromatography (HPLC). There is also great interest in the technological processes involved in the production of dry extracts of this native medicinal plant with the primary goal of assuring the quality of phytopharmaceutical products.

En esta revisión se describen las características botánicas, químicas, farmacológicas y fitotecnologicas de Passiflora alata Curtis, con énfasis en los métodos analíticos. Originaria de Brasil, varias preparaciones farmacéuticas de P. alata son registradas por el organismo regulador ANVISA. En tres de las cinco ediciones de la Farmacopea Brasileña, las hojas de P. alata se han incluido bajo la denominación de "maracuyá" (fruta de la pasión). Esta especie debe ser citada como Passiflora alata Curtis, publicada originalmente en 1788 en “Botanical Magazine”. En la última década, los estudios fitoquímicos y farmacológicos de investigadores brasileños relacionados con esta planta han aumentado substancialmente. A pesar de varios estudios, las sustancias responsables de las actividades ansiolítica, sedante, antioxidante y antiulcerosa atribuidas a la passiflora continúan siendo desconocidos. Los métodos analíticos para la cuantificación de los marcadores están siendo desarrollados con el fin de mejorar el análisis de control de calidad y para comprender mejor la relación entre marcadores químicos y sus efectos farmacológicos. Estos métodos incluyen espectrometría de alto rendimiento, cromatografía en capa fina (HPTLC) y la cromatografía líquida de alta resolución (HPLC). También existe un gran interés en los procesos tecnológicos envueltos en la producción de extractos secos con el objetivo principal de asegurar la calidad de los productos fitosanitarios.

Phylogenetic and virulence analysis of tick-borne encephalitis virus field isolates from Switzerland.

Tick-borne encephalitis (TBE) is an endemic disease in Switzerland, with about 110-120 reported human cases each year. Endemic areas are found throughout the country. However, the viruses circulating in Switzerland have not been characterized so far. In this study, the complete envelope (E) protein sequences and phylogenetic classification of 72 TBE viruses found in Ixodes ricinus ticks sampled at 39 foci throughout Switzerland were analyzed. All isolates belonged to the European subtype and were highly related (mean pairwise sequence identity of 97.8% at the nucleotide and 99.6% at the amino acid level of the E protein). Sixty-four isolates were characterized in vitro with respect to their plaque phenotype. More than half (57.8%) of isolates produced a mixture of plaques of different sizes, reflecting a heterogeneous population of virus variants. Isolates consistently forming plaques of small size were associated with recently detected endemic foci with no or only sporadic reports of clinical cases. All of six virus isolates investigated in an in vivo mouse model were highly neurovirulent (100% mortality) but exhibited a relatively low level of neuroinvasiveness, with mouse survival rates ranging from 50% to 100%. Therefore, TBE viruses circulating in Switzerland belong to the European subtype and are closely related. In vitro and in vivo surrogates suggest a high proportion of isolates with a relatively low level of virulence, which is in agreement with a hypothesized high proportion of subclinical or mild TBE infections.

High-throughput procedure for tick surveys of tick-borne encephalitis virus and its application in a national surveillance study in Switzerland.

Tick-borne encephalitis (TBE), a viral infection of the central nervous system, is endemic in many Eurasian countries. In Switzerland, TBE risk areas have been characterized by geographic mapping of clinical cases. Since mass vaccination should significantly decrease the number of TBE cases, alternative methods for exposure risk assessment are required. We established a new PCR-based test for the detection of TBE virus (TBEV) in ticks. The protocol involves an automated, high-throughput nucleic acid extraction method (QIAsymphony SP system) and a one-step duplex real-time reverse transcription-PCR (RT-PCR) assay for the detection of European subtype TBEV, including an internal process control. High usability, reproducibility, and equivalent performance for virus concentrations down to 5 x 10(3) viral genome equivalents/microl favor the automated protocol compared to the modified guanidinium thiocyanate-phenol-chloroform extraction procedure. The real-time RT-PCR allows fast, sensitive (limit of detection, 10 RNA copies/microl), and specific (no false-positive test results for other TBEV subtypes, other flaviviruses, or other tick-transmitted pathogens) detection of European subtype TBEV. The new detection method was applied in a national surveillance study, in which 62,343 Ixodes ricinus ticks were screened for the presence of TBE virus. A total of 38 foci of endemicity could be identified, with a mean virus prevalence of 0.46%. The foci do not fully agree with those defined by disease mapping. Therefore, the proposed molecular test procedure constitutes a prerequisite for an appropriate TBE surveillance. Our data are a unique complement of human TBE disease case mapping in Switzerland.