Different drug approaches to COVID-19 treatment worldwide: an update of new drugs and drugs repositioning to fight against the novel coronavirus.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine's effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

Metabolic profiling of Candida clinical isolates of different species and infection sources.

Candida species are the most common cause of opportunistic fungal infections. Rapid identification and novel approaches for the characterization of these fungi are of great interest to improve the diagnosis and the knowledge about their pathogenic properties. This study aimed to characterize clinical isolates of Candida spp. by proteomics (MALDI-TOF MS) and metabolomics (1H-NMR), and to correlate their metabolic profiles with Candida species, source of infection and different virulence associated parameters. In particular, 49 Candida strains from different sources (blood, n = 15; vagina, n = 18; respiratory tract, n = 16), belonging mainly to C. albicans complex (61%), C. glabrata (20%) and C. parapsilosis (12%) species were used. Several extracellular and intracellular metabolites showed significantly different concentrations among isolates recovered from different sources of infection, as well as among different Candida species. These metabolites were mainly related to the glycolysis or gluconeogenesis, tricarboxylic acid cycle, nucleic acid synthesis and amino acid and lipid metabolism. Moreover, we found specific metabolic fingerprints associated with the ability to form biofilm, the antifungal resistance (i.e. caspofungin and fluconazole) and the production of secreted aspartyl proteinase. In conclusion, 1H-NMR-based metabolomics can be useful to deepen Candida spp. virulence and pathogenicity properties.

Leishmanicidal and antimicrobial activity of primin and primin-containing extracts from Miconia willdenowii.

As a part of an ongoing bioprospective project, searching for potential medicinal plants from the Brazilian Atlantic Forest, Miconia willdenowii was selected for its potential leishmanicidal and antimicrobial activities. The crude ethanolic extract of M. willdenowii showed an inhibition of 99.7% of the promastigote forms of Leishmania amazonensis at the concentration of 80 µg/mL. Further investigation of its antimicrobial activity against pathogenic fungi and Gram positive and negative bacteria, revealed a significant antimicrobial activity. A bioguided study with its liquid-liquid partition fractions revealed the hexane fraction (Hex) as the most active against Leishmania, inhibiting 99.2% and 46.9% of the protozoan at concentrations of 40 and 20 µg/mL, respectively. Hex also showed significant antimicrobial activity against Staphylococcus aureus and Candida krusei with IC50 of 15.6 and 62.5 µg/mL, respectively. Purification of Hex led to the isolation of 2-methoxy-6-pentyl-benzoquinone (1, also known as primin) as the active metabolite, probably responsible for the observed antimicrobial and anti-leishmania effects. Primin (1) disclosed leishmanicidal activity (IC50 = 1.25 µM), showing higher potency than the standard drug amphotericin B (IC50 = 5.08 µM), with additional antifungal effects against all tested fungi species. Compound 1 also showed significant activity against S. aureus (IC50 = 8.94 µM), showing a comparable potency with the reference drug chloramphenicol (IC50 = 6.19 µM), but with a potential cytotoxicity towards peripheral human blood mononuclear cells (CC50 = 255.15 µM). Here in, the antimicrobial and anti-L. amazonensis effects of M. willdenowii are reported for the first time, as well as Primin (1) as its probable bioactive metabolite.

Candida spp. and phagocytosis: multiple evasion mechanisms.

Invasive fungal infections are a global health problem, mainly in hospitals, where year by year hundreds of patients die because of these infections. Commensal yeasts may become pathogenic to human beings, affecting mainly immunocompromised patients. During infectious processes, the immune system uses phagocytes to eliminate invader microorganisms. In order to prevent or neutralize phagocyte attacks, pathogenic yeasts can use virulence factors to survive, as well as to colonize and infect the host. In this review, we describe how Candida spp., mainly Candida albicans, interact with phagocytes and use several factors that contribute to immune evasion. Polymorphism, biofilm formation, gene expression and enzyme production mediate distinct functions such as adhesion, invasion, oxidative stress response, proteolysis and escape from phagocytes. Fungal and human cells have similar structures and mechanisms that decrease the number of potential targets for antifungal drugs. Therefore, research on host-pathogen interaction may aid in the discovery of new targets and in the development of new drugs or treatments for these diseases and thus to save lives.

Ozone against Pseudomonas aeruginosa biofilms in contact lenses storage cases.

Pseudomonas aeruginosa is associated with ocular infections such as keratitis. Multipurpose contact lens solutions can be used for washing, disinfection and storage of contact lenses, however, P. aeruginosa biofilm disinfection by this method is unsatisfactory. The present study aimed to investigate the effectiveness of ozonated water in reducing P. aeruginosa colony count. Lenses kept in storage cases were contaminated with P. aeruginosa and disinfected using ozonized water, chlorhexidine, ultrasound and multipurpose solutions. The multipurpose solutions and ultrasound methods reduced colony count from 1.17 to 1.63 log10 CFU/cm2 (92.93% to 97.31%), respectively, of P. aeruginosa biofilm cell viability when compared to the positive control. Both, ozonated water and chlorhexidine showed 7.42 log reduction in the number of viable cells of P. aeruginosa biofilm. As compared to chlorhexidine, ozonized water did not depose any known toxic residues, so that we recommend it as an alternative disinfectant solution for contact lenses storage cases.

Conhecimento dos agentes comunitários de saúde sobre segurança alimentar e intervenção / Community health agents' knowledge about food safety and an intervention

As doenças de origem alimentar constituem um dos mais sérios problemas de saúde pública no mundo atual. Os profissionais envolvidos com a atenção primária em saú- de, incluindo aqueles do Programa de Saúde da Família (PSF), podem contribuir significativamente para a promo- ção de hábitos saudáveis na higiene e preparo dos alimentos, orientando à população para a segurança alimentar. Todavia, o despreparo de muitos Agentes Comunitários de Saúde (ACS) dificulta a prevenção, identificação e notificação de surtos de toxinfecções alimentares. Esta pesquisa teve por objetivo avaliar o conhecimento de ACS sobre segurança alimentar e paralelamente, realizar intervenção educativa. Constatou-se que há deficiências na capacitação destes profissionais para lidar com a prevenção e controle das doenças de origem alimentar. Entretanto, após a intervenção educativa, verificou-se o aumento do conhecimento dos ACS sobre segurança alimentar, higiene e boas práticas de manipulação.

Foodborne diseases constitute one of the most serious public health problems in the world today. The professionals involved in primary health care, including those from the Family Health Program (FHP), can contribute significantly to the promotion of healthy habits in hygiene and food preparation, guiding the population to food security. However, the unpreparedness of many Community Health Agents (CHAs) hinders the prevention, identification, and reporting of foodborne disease outbreaks. This study aimed to evaluate the knowledge of CHAs about food security and, in parallel, conduct an educational intervention. It was verified that there are deficiencies in the training of these professionals toward dealing with the prevention and control of foodborne diseases. However, after the educational intervention, an increase was observed in the CHAs' knowledge about food safety, hygiene, and good handling practices.