For billions of years, the phenomena of life and biocatalysis have been intertwined. If in the beginning biocatalysis was fundamental for the origin of life, currently it is very important for the cleaner production of pharmaceuticals and fine chemical intermediates. There is no doubt that drugs have brought great benefits to humanity, but currently, the expectations of modern society are focused on drugs with greater safety, less environmental impact, more sustainable practices, and less energy use. This review intends to show how the challenges for the production of some low molecular weight drugs produced by synthetic routes that involve at least one biotechnological step using microorganisms or enzymes were faced. These biotechnological drug production routes are more sustainable than conventional synthetic routes, as they produce a much smaller amount of waste, use moderate reaction conditions, have lower energy consumption, and have lower metal consumption, in addition to being more selective. Additionally, many natural products have structures too complex to be produced exclusively by chemical routes. The large-scale and economical production of these drugs is of great importance for fighting cancer as well as inflammatory, infectious, autoimmune, metabolic, hormonal, cardiovascular, and neurological diseases, among others.

RESUMO Objetivo. Identificar estudos sobre a competência dos mosquitos Culex como vetores da transmissão do vírus Zika em todo o mundo. Métodos. Uma revisão integrativa foi realizada para identificar artigos relevantes sobre experimentos específicos para determinar se os mosquitos Culex são vetores do vírus Zika. As fontes utilizadas na pesquisa foram o portal eletrônico CAPES (MEDLINE/PubMed, ScienceDirect Journals, Nature Publishing Group, Sci-ELO, Springer Link, e outras 250 bases de dados) e a literatura cinza. Resultados. Foram identificados 344 artigos, dos quais 36 foram considerados para esta revisão. Oito artigos relataram infecção nas glândulas salivares de Culex quinquefasciatus, Culex restuans, Culex tarsalis e Culex coronator. Culex quinquefasciatus foi a espécie mais estudada entre as confirmadas como vetores potenciais do vírus Zika. Apenas as linhagens asiáticas (THA / 2014 / SV0127-14; SZ01 [2016]) e americanas (BRPE243 [2015]; PRVABC59 [2015]) podem infectar as glândulas salivares dos mosquitos Culex. As cepas africanas analisadas (MR766 e DAK AR 41525) não foram capazes de infectar as glândulas salivares. Conclusões. Ainda não há evidências convincentes para indicar que os mosquitos Culex são um vetor competente do vírus Zika. Contudo, estudos adicionais de monitoramento devem ser realizados, especialmente no que diz respeito à transmissão do vírus Zika para outras espécies de mosquitos. Além disso, os estudos não devem se limitar a estudar a infecção nas glândulas salivares.

ABSTRACT Objective. To identify studies on the competence of Culex mosquitoes as vectors for the transmission of Zika virus (ZIKV) around the globe. Methods. We performed an integrative review to identify relevant articles on specific experiments to determine whether Culex mosquitoes are vectors for ZIKV. The sources we used for our research were the Brazilian Periódicos CAPES electronic portal (MEDLINE/PubMed, ScienceDirect Journals, Nature Publishing Group, SciELO, Springer Link, and 250 other databases) and gray literature. Results. We identified 344 studies, of which 36 were considered for this review. In 8 studies, infection in salivary glands of Culex quinquefasciatus, Culex restuans, Culex tarsalis, and Culex coronator was detected. Cx. quinquefasciatus was the most studied among those confirmed as potential ZIKV vectors, and only strains of Asian lineages (THA/2014/SV0127-14; SZ01 (2016)) and American lineages (BRPE243 (2015); PRVABC59 (2015)) can infect the salivary glands of Culex mosquitoes. The tested African strains (MR766 and DAK AR 41525) were unable to infect salivary glands. Conclusions. There is still a lack of compelling evidence that indicates Culex spp. are a competent ZIKV vector, but they should remain a target for further monitoring studies, especially regarding ZIKV transmission to other species. Furthermore, studies should not be limited to studying whether their salivary glands are infected.

RESUMEN Objetivo. Identificar estudios sobre la competencia de los mosquitos Culex como vectores de la transmisión del virus del Zika en todo el mundo. Métodos. Se realizó una revisión integradora para identificar artículos relevantes sobre experimentos específicos dirigidos a determinar si los mosquitos Culex son vectores del virus del Zika. Se emplearon fuentes obtenidas a partir del portal electrónico de revistas CAPES (MEDLINE/PubMed, ScienceDirect Journals, Nature Publishing Group, SciELO, Springer Link, y otras 250 bases de datos) y la literatura gris. Resultados. Se identificaron 344 estudios, 36 de los cuales fueron considerados para esta revisión. En 8 estudios se detectó infección en las glándulas salivales de Culex quinquefasciatus, Culex restuans, Culex tarsalis y Culex coronator. Cx. quinquefasciatus fue la especie más estudiada entre las confirmadas como potenciales vectores del virus del Zika, y solo las cepas de linajes asiáticos (THA/2014/SV0127-14; SZ01 [2016]) y americanos (BRPE243 [2015]; PRVABC59 [2015]) pueden infectar las glándulas salivales de los mosquitos Culex. Las cepas africanas analizadas (MR766 y DAK AR 41525) no fueron capaces de infectar las glándulas salivales. Conclusiones. Aunque faltan pruebas convincentes que indiquen que las especies de Culex spp. son un vector competente del virus del Zika, estas deben seguir monitoreándose mediante estudios adicionales, especialmente respecto de su capacidad para transmitir el virus del Zika a otras especies. Esta vigilancia no debería limitarse solamente a determinar la infección en las glándulas salivales.

RESUMO A Organização Mundial da Saúde (OMS) foi informada, em dezembro de 2019, sobre um surto de pneumonia por coronavírus em Wuhan, província de Hubei (China). Posteriormente, em 12 de março de 2020, 125 048 casos e 4 614 mortes haviam sido registrados. O coronavírus é um vírus RNA envelopado do gênero Betacoronavírus, distribuído em aves e em humanos e outros mamíferos. A OMS designou a nova doença por coronavírus como COVID-19. Mais de 80 ensaios clínicos foram iniciados para testar tratamentos para o coronavírus, incluindo alguns de reposicionamento de medicamentos para o COVID-19. Assim, em março de 2020 realizou-se uma busca na base de dados clinicaltrials.gov. Os critérios de elegibilidade para os estudos recuperados foram: conter o número identificador da base de dados clinicaltrials.gov; descrever o número de participantes e o período do estudo; descrever as condições clínicas dos participantes; e utilizar intervenções para tratamento de doentes infectados com o novo coronavírus SARS-CoV-2 (2019-nCoV) com medicamentos já estudados ou aprovados para qualquer outra doença. É essencial salientar que este artigo apenas capturou ensaios listados na base de dados clinicaltrials.gov. Foram identificados 24 ensaios clínicos envolvendo mais de 20 medicamentos, tais como imunoglobulina humana, interferons, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumabe e medicamentos chineses tradicionais. Embora o reposicionamento de medicamentos tenha algumas limitações, os ensaios clínicos de reposicionamento podem representar uma estratégia atraente, porque facilitam a descoberta de novas classes de medicamentos, têm custos mais baixos, levam menos tempo para chegar ao mercado e se beneficiam de cadeias de fornecimento farmacêutico já existentes para formulação e distribuição.

ABSTRACT The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.

RESUMEN En diciembre de 2019 fue informado a la Organización Mundial de la Salud (OMS) un brote de neumonía por coronavirus en Wuhan, provincia de Hubei, China. Al 12 de marzo de 2020, se habían notificado 125 048 casos y 4 614 muertes. El coronavirus es un virus ARN envuelto del género Betacoronavirus distribuido en aves, seres humanos y otros mamíferos. La OMS ha denominado a la nueva enfermedad por coronavirus COVID-19. Se han puesto en marcha más de 80 ensayos clínicos para evaluar un tratamiento para el coronavirus, que incluyen algunos ensayos de reposicionamiento de medicamentos para la COVID-19. En marzo de 2020 se llevó a cabo una búsqueda de los ensayos clínicos registrados en la base de datos clinicaltrials.gov. Los criterios de elegibilidad para los estudios recuperados fueron tener un número de identificación de la base de datos clinicaltrials.gov; describir el número de participantes y el período del estudio; describir las condiciones clínicas de los participantes; y emplear intervenciones con medicamentos ya estudiados o aprobados para cualquier otra enfermedad en pacientes infectados con el nuevo coronavirus SARS-CoV-2 (2019-nCoV). Es esencial destacar que este artículo solo recoge los ensayos que figuran en la base de datos clinicaltrials. gov. Se identificaron 24 ensayos clínicos relacionados con más de 20 medicamentos, como inmunoglobulina humana, interferones, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumab y medicina tradicional china. Aunque el reposicionamiento de medicamentos tiene algunas limitaciones, el reposicionamiento de los ensayos clínicos puede representar una estrategia atractiva porque facilita el descubrimiento de nuevas clases de medicamentos; estos tienen costos más bajos y tardan menos en llegar al mercado; y existen cadenas de suministro farmacéutico que apoyan la formulación y la distribución.

Vários estudos têm mostrado o potencial citotóxico de derivados da nor-β-lapachona contra células tumorais. Considerando a nor-β-lapachona um importante protótipo, uma série inédita de nor-β-lapachonas substituídas em C-3 foi sintetizada através de uma nova metodologia sintética envolvendo intermediário sintético 3-hidróxi-nor-β-lapachona para o acoplamento de alguns nucleófilos contendo núcleos derivados de carboidratos ou 2H-pirazóis. Todos os derivados foram avaliados frente a quatro linhagens de células tumorais. Duas das substâncias apresentaram moderada citotoxicidade, enquanto as demais inibiram fortemente todas as linhagens tumorais testadas.

Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.

Plant extracts of Eugenia punicifolia (Kunth) DC., Myrtaceae, are used in Amazon region of Brazil to treat diarrhea and stomach disturbances, and as hypoglycemic medicine. We have recently shown that an aqueous extract of E. punicifolia augmented cholinergic neurotransmission in a rat phrenic nerve-diaphragm preparation. In this study, we investigated the effects of an E. punicifolia dichloromethane extract (EPEX) in a neuronal model of cholinergic neurotransmission, the bovine adrenal chromaffin cell. EPEX augmented the release of catecholamine triggered by acetylcholine (ACh) pulses but did not enhance ACh-evoked inward currents, which were inhibited by 30%. Since EPEX did not cause a blockade of acetylcholinesterase or butyrylcholinesterase, it seems that EPEX is not directly activating the cholinergic system. EPEX also augmented K+-elicited secretion without enhancing the whole-cell inward calcium current. This novel and potent effect of EPEX in enhancing exocytosis might help to identify the active component responsible for augmenting exocytosis. When elucidated, the molecular structure of this active principle could serve as a template to synthesise novel compounds to regulate the exocytotic release of neurotransmitters.