The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Biodistribution and Tumor Targeted Accumulation of Anti-CEA-loaded Iron Nanoparticles.

INTRODUCTION: Active targeting of tumors by nanomaterials favors early diagnosis and the reduction of harsh side effects of chemotherapeuticals. METHOD: We synthesized magnetic nanoparticles (64 nm; -40 mV) suspended in a magnetic fluid (MF) and decorated them with anti-carcinoembryonic antigen (MFCEA; 144 nm; -39 mV). MF and MFCEA nanoparticles were successfully radiolabeled with technetium-99m (99mTc) and intravenously injected in CEA-positive 4T1 tumor-bearing mice to perform biodistribution studies. Both 99mTc-MF and 99mTc-MFCEA had marked uptake by the liver and spleen, and the renal uptake of 99mTc-MFCEA was higher than that observed for 99mTc-MF at 20h. At 1 and 5 hours, the urinary excretion was higher for 99mTc-MF than for 99mTc-MFCEA. RESULTS: These data suggest that anti-CEA decoration might be responsible for a delay in renal clearance. Regarding the tumor, 99mTc-MFCEA showed tumor uptake nearly two times higher than that observed for 99mTc-MFCEA. Similarly, the target-nontarget ratio was higher with 99mTc-MFCEA when compared to the group that received the 99mTc-MF. CONCLUSION: These data validated the ability of active tumor targeting by the as-developed antiCEA loaded nanoparticles and are very promising results for the future development of a nanodevice for the management of breast cancer and other types of CEA-positive tumors.

Jelleine, a Family of Peptides Isolated from the Royal Jelly of the Honey Bees (Apis mellifera), as a Promising Prototype for New Medicines: A Narrative Review.

The jelleine family is a group of four peptides (jelleines I-IV) originally isolated from the royal jelly of honey bee (Apis mellifera), but later detected in some honey samples. These oligopeptides are composed of 8-9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38-50% of hydrophobic residues and a carboxamide C-terminus. Jelleines, generated by processing of the C-terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I-III have promising antimicrobial activity and low toxicity (LD50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use.

Therapeutic Prospection of Animal Venoms-Derived Antimicrobial Peptides against Infections by Multidrug-Resistant Acinetobacter baumannii: A Systematic Review of Pre-Clinical Studies.

Infections caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) have become a public health emergency. Due to the small therapeutic arsenal available to treat these infections, health agencies have highlighted the importance of developing new antimicrobials against MDR-Ab. In this context, antimicrobial peptides (AMPs) stand out, and animal venoms are a rich source of these compounds. Here, we aimed to summarize the current knowledge on the use of animal venom-derived AMPs in the treatment of MDR-Ab infections in vivo. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eight studies included in this review identified the antibacterial activity of eleven different AMPs against MDR-Ab. Most of the studied AMPs originated from arthropod venoms. In addition, all AMPs are positively charged and rich in lysine residues. In vivo assays showed that the use of these compounds reduces MDR-Ab-induced lethality and bacterial load in invasive (bacteremia and pneumonia) and superficial (wounds) infection models. Moreover, animal venom-derived AMPs have pleiotropic effects, such as pro-healing, anti-inflammatory, and antioxidant activities, that help treat infections. Animal venom-derived AMPs are a potential source of prototype molecules for the development of new therapeutic agents against MDR-Ab.

Antifungal activity of a shortened analogue of the natural peptide LyeTx I isolated from the venom of the spider Lycosa erythrognatha.

The increase in the incidence of fungal infections associated with the limited therapeutic arsenal available and the increasing rate of resistance of pathogenic fungi reinforce the need for research of new antifungal agents. Thus, this study aims to evaluate the antifungal activity of the peptide LyeTx I mnΔK, a shortened analogue of the natural peptide LyeTx I derived from spider venom, against Candida species. LyeTx I mnΔK showed potent activity against Candida spp. with minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) between 4 and 32 µM. The peptide also completely inhibited the yeast-to-hypha transition (at 2 µM) and broke mature biofilms (67% reduction at 32 µM) of C. albicans. In addition, LyeTx I mnΔK did not induce resistance in C. albicans during 21 days of exposure. Therefore, the LyeTx I mnΔK is a promising prototype for the development of new antifungal agents.

Study of the influence of fecal material on the prognosis of intra-abdominal candidiasis using a murine model of technetium-99 m (99 mTc)-Candida albicans.

Intra-abdominal candidiasis (IAC) occurs due to the direct inoculation of Candida into the sterile peritoneal cavity or leakage of the gastrointestinal tract. An important difference between the two forms of the disease is the presence of fecal material, which is exclusive to the latter condition. However, the influence of fecal material on the prognosis of IAC is still poorly understood. Furthermore, methodologies that use the quantification of fungal load by culture methods have low sensitivity, as they do not adequately show the precocity of the infectious process. Here, we developed a new method to evaluate the aspects of the pathophysiology of IAC, mainly the influence of fecal material on the prognosis of infection, by using C. albicans radiolabeled with technetium-99 m (99 mTc). C. albicans was successfully radiolabeled with 99 mTc (18.5 MBq) using dihydrate stannous chloride (100 µM) as a reducing agent. This binding was stable for 72 h. Viability, yeast-to-hyphae transition, morphology, and antifungal susceptibility were not altered by radiolabeling C. albicans with 99 mTc. The biomass and the fungal load of 99 mTc-C. albicans biofilms were reduced compared to the C. albicans non-radiolabeled after 72 h and 48 h of incubation, respectively. In the IAC model, the fungal load in the biodistribution of 99 mTc-C. albicans and culture assays was higher in animals receiving fungal inoculum without fecal material, suggesting that the presence of this component reduces the invasiveness of the pathogen.

Aminoglycoside resistance in domestic sewage and clinical Escherichia coli isolates

SUMMARY Introduction: Escherichia coli, a Gram-negative bacillus, is found in diverse environments and causes several human diseases, such as pneumonia and urinary tract infections. Aminoglycosides are antimicrobials that present high activity against Gram-negative species, including multidrug-resistant pathogens. However, the indiscriminate use of these compounds has selected resistant microorganisms, mainly due to the production of aminoglycoside-modifying enzymes (AME). Material and methods: The minimal inhibitory concentration of the aminoglycosides amikacin, gentamicin, and neomycin against clinical (CI, n = 52, only urinary) and domestic sewage (DS, n = 33) E. coli isolates was determined by the microdilution method, according to the European Committee on Antimicrobial Susceptibility Testing. The presence of AMEs among E. coli isolates was determined based on the susceptibility profile to amikacin, gentamicin, kanamycin, and tobramycin, according to Mancini et al. (2019). Results: Overall, 33.3% of the DS isolates and 100% of the CI isolates presented mechanisms of resistance to amikacin, gentamicin, or neomycin. The extended-spectrum beta-lactamase enzymes-producing isolates (23/27, 85%) showed mechanisms of resistance to gentamicin and/or neomycin and resistance to amikacin was simultaneously observed only in CI isolates. All DS isolates were considered wild-type-no AME, while APH (3') (14/52) and AAC (3') (10/52) enzymes were detected among CI isolates, one of which produces APH (3') and AAC (6')-I simultaneously. Conclusion: Resistance to aminoglycosides is present among E. coli isolates in Brazil, but to a lesser extent in environmental isolates. Besides, AMEs are frequent in CI isolates, and surveillance for antimicrobial resistance should be implemented to monitor aminoglycoside-resistant E. coli infections.

Introducción: Escherichia coli se encuentra en diversos ambientes y causa enfermedades humanas. Los aminoglucósidos son antimicrobianos que presentan actividad contra especies gramnegativas. Sin embargo, el uso indiscriminado de estos compuestos ha seleccionado microorganismos resistentes, principalmente debido a la producción de enzimas modificadoras de aminoglucósidos (AME). Material y métodos: La concentración mínima inhibitoria de aminoglucósidos frente a aislados de E.coli clínicos (CI, n = 52) y de aguas residuales sanitarias (DS, n = 33) se determinó mediante el método de microdilución, según la European Committee on Antimicrobial Susceptibility Testing. La presencia de AME se determinó con base en el perfil de susceptibilidad a amikacina, gentamicina, kanamicina y tobra-micina, según Mancini et al. (2019). Resultados: 33,3% de los aislados de DS y 100% de los CI presentaron resistencia a amikacina, gentamicina o neomicina. Los aislados productores de enzimas betalactamasas de espectro extendido (23/27, 85%) mostraron resistencia a gentamicina y/o neomicina y la resistencia a amikacina se observó simultáneamente solo en CI. Todos los aislados de DS se consideraron wild type sin AME, mientras que las enzimas APH (3') (14/52) y AAC (3') (10/52) se detectaron entre CI, uno de los cuales produce APH (3') y AAC (6')-I simultáneamente. Conclusión: La resistencia a los aminoglucósidos está presente entre los aislados de E. coli en Brasil, pero en menor grado en los aislados ambientales. Se debe implementar la vigilancia de la resistencia a los antimicrobianos para monitorear las infecciones por E. coli resistentes a los aminoglucósidos.

SUMÁRIO Introdução: Escherichia coli é encontrada em vários ambientes e causa doenças em humanos. Os aminoglicosídeos são antimicrobianos que exibem atividade contra espécies Gram-negativas. No entanto, o uso indiscriminado desses compostos tem selecionado microrganismos resistentes, principalmente devido à produção de enzimas modificadoras de aminoglicosídeos (EMA). Material e métodos: A concentração inibitória mínima de aminoglicosídeos contra isolados de E. coli recuperadas de amostras clínicas (IC, n=52) e de águas residuais sanitárias (AR, n=33) foi determinada pelo método de microdiluição, de acordo com o European Committee on Antimicrobial Susceptibility Testing. A presença de EMA foi determinada com base no perfil de suscetibilidade à amicacina, gentamicina, canamicina e tobramicina, de acordo com Mancini et al. (2019). Resultados: 33,3% dos ARS e 100% dos ICs apresentaram resistência à amicacina, gentamicina ou neomicina. Os isolados produtores de enzima beta-lactamase de espectro estendido (23/27, 85%) mostraram resistência à gentamicina e/ou neomicina e resistência à amicacina foi observada simultaneamente apenas em um IC. Todos os ARs foram considerados de tipo selvagem sem EMA, enquanto as enzimas APH (3') (14/52) e AAC (3') (10/52) foram detectadas entre os ICs, um dos quais produz APH (3') e AAC (6')-I simultaneamente. Conclusão: A resistência aos aminoglicosídeos está presente entre isolados clínicos de E. coli no Brasil, mas em menor grau em isolados ambientais. Assim a vigilância da resistência antimicrobiana deve ser implementada para monitorar infecções por E. coli resistentes aos aminoglicosídeos.

Capacidade de formação de biofilmes e perfil de resistência de Acinetobacter baumannii isolados em unidades de terapia intensiva: uma revisão sistemática

Introdução: Acinetobacter baumanni é um cocobacilo Gram negativo responsável por elevadas taxas de infecções relacionadas à assistência à saúde (IRAS). Apresenta alto nível de resistência intrínseca a antimicrobianos, além da capacidade de adquirir resistência a carbapenêmicos e polimixinas. Ainda, A. baumannii possui habilidade para produzir biofilmes em superfícies abióticas e bióticas, o que favorece a infecção de pacientes gravemente enfermos internados em unidades de terapia intensiva (UTI). Deve ser ressaltado que bactérias envolvidas em biofilmes apresentam maior resistência aos antimicrobianos, atribuída a fatores bioqúmicos, moleculares e as condições dos hospedeiros, o que dificulta o tratamento dessas infecções. Objetivos: Avaliar a produção de biofilme por isolados de A. baumannii recuperados de pacientes internados em UTIs, bem como operfil de susceptibilidade a antimicrobianos (aminoglicosídeos, tigeciclina, carbapenêmicos e polimixinas) entre esses isolados. Métodos: Foi realizada uma revisão sistemática de acordo com os critérios Prisma nos bancos de dados Pubmed/Medline, Scopus, Lilacs, Scielo, e Web of Science. Resultados: Foram incluídos um total de 12 artigos que avaliaram 1006 isolados clínicos de A. baumannii, os quais todos foram resistentes aos carbapenê-micos. No entanto, a maioria dos isolados permaneceu sensível as polimixinas B e E(94,46%). A porcentagem dos isolados produtores de biofilme foi alta (96,3%), e neste estudo não fica clara a relação entre a habilidade de produzir biofilmes e a resistência aos antimicrobianos analisados. Conclusão: Mais estudos devem ser conduzidos para monitorar a resistência aos antimicrobianos em A. baumannii, sobretudo em produtores de biofilme, visto que o manejo terapêutico das infecções ocasionadas por essas linhagens torna-se mais complexo e desafiador.

SUMMARY Introduction: Acinetobacter baumanni is a Gram-negative coccobacillus responsible for high rates of healthcare-related infections (HAI). It has a high level of intrinsic resistance to antimicrobials, in addition to the ability to acquire resistance to carbapenems and polymyxins. Furthermore, A. baumannii has the ability to produce biofilms on abiotic and biotic surfaces, which favors the infection of critically ill patients admitted to intensive care units (ICU). It should be noted that bacteria involved in biofilms have greater resistance to antimicrobials, attributed to biochemical and molecular factors and the conditions of the hosts, which makes the treatment of these infections difficult. Objectives: To evaluate the biofilm production by A. baumannii isolates recovered from ICU patients, as well as the antimicrobial susceptibility profile (aminoglycosides, tigecycline, carbapenems and polymyxins) among these isolates. Methods: A systematic review was performed according to PRISMA criteria in the PUBMED/MEDLINE, Scopus, LILACS, SciELO, and Web of Science databases. Results: A total of 12 articles that evaluated 1006 clinical isolates of A. baumannii, all of which were resistant to carbapenems, were included. However, most isolates remained sensitive to polymyxins B and E (94.46%). The percentage of biofilm-producing isolates was high (96.3%), and in this study the relationship between the ability to produce biofilms and resistance to the analyzed antimicrobials is not clear. Conclusion: More studies should be conducted to monitor antimicrobial resistance in A. baumannii, especially in biofilm producers, as the therapeutic management of infections caused by these strains becomes more complex and challenging.

Introducción: Acinetobacter baumanni es un cocobacilo gramnegativo responsable de altas tasas de infecciones relacionadas con la salud. Tiene un alto nivel de resistencia intrínseca a los antimicrobianos, además de la capacidad de adquirir resistencia a los carbapenémicos y polimixinas. Además, A. baumannii tiene la capacidad de producir biopelículas en superficies abióticas y bióticas, lo que favorece la infección de pacientes críticos ingresados en unidades de cuidados intensivos (UCI). Cabe señalar que las bacterias involucradas en biofilms tienen mayor resistencia a los antimicrobianos, atribuida a factores bioquímicos y moleculares y a las condiciones de los hospedadores, lo que dificulta el tratamiento de estas infecciones. Objetivos: Evaluar la producción de biofilm por aislamientos de A. baumannii recuperados de pacientes de UCI, así como el perfil de susceptibilidad antimicrobiana (amino-glucósidos, tigeciclina, carbapenémicos y polimixinas) entre estos aislamientos. Métodos: Se realizó una revisión sistemática según los criterios Prisma en las bases de datos Pubmed / Medline, Scopus, Lilacs, SciELO y Web of Science. Resultados: Se incluyeron un total de 12 artículos que evaluaron 1006 aislamientos clínicos de A. baumannii, todos ellos resistentes a carbapenémicos. Sin embargo, la mayoría de los aislados permanecieron sensibles a las polimixinas B y E (94,46%). El porcentaje de aislamientos productores de biopelículas fue alto (96,3%), y en este estudio no está clara la relación entre la capacidad de producir biopelículas y la resistencia a los antimicrobianos analizados. Conclusión: Se deben realizar más estudios para monitorear la resistencia a los antimicrobianos en A. baumannii, especialmente en productores de biopelículas, ya que el manejo terapéutico de las infecciones causadas por estas cepas se vuelve más complejo y desafiante.

Mechanisms involved in resistance to carbapenems among Acinetobacter baumannii isolates recovered in Brazil: A systematic review and meta-analysis

SUMMARY Introduction: Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a health problem due to the limited therapeutic options available. This study was carried out to evaluate the main mechanisms of resistance of carbapenems in CRAB in the last 10 years in Brazil and to describe the susceptibility profile to tigecycline and polymyxins in these isolates. Material and methods: A systematic review was carried out according to Prisma in PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) and Cochrane Library. Data regarding enzyme resistance to carbapenems were evaluated by meta-analysis according to the random effect. Results: 21 articles were selected according to inclusion and exclusion criteria that evaluated 1096 CRAB. Most of the studies were carried out in the southern (33.3 %) and southeast (23.8 %) regions of Brazil (33.3 %) and in 2016 and 2018. According to the meta-analyzes, OXA-type carbapenemase was the main mechanism involved in the low susceptibility to carbapenems in CRAB (98%; 95% CI: 0.91, 0.99; I2 = 95%), with bla OXA-23-like (91 %; 95 % CI: 0.76; 0.97; I2 = 97 %) or bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0.15, 0.99; I2 = 98 %) genes, followed by metallo-ß-lactamases (MBL) (12 %, 95 % CI: 0.09, 0.15, I2 = 99 %) and Klebsiella pneumoniae carbapenemase (KPC) (6 %, 95 % CI: 0.04; 0.08; I2 = 87 %). Conclusion: The included studies showed that susceptibility to colistin (99 %) and tigecy-cline (93 %) remains high and was not affected by carbapenem resistance.

Introducción: Las infecciones por Acinetobacter baumannii resistente a carbapenémicos (CRAB) es un problema de salud debido a las limitadas opciones terapéuticas disponibles. Este estudio se realizó para evaluar los principales mecanismos de resistencia de los carbapenémicos en CRAB en los últimos 10 años en Brasil y describir el perfil de susceptibilidad a tigeciclina y polimixinas en estos aislados. Material y métodos: Se realizó una revisión sistemática de acuerdo con Prisma en PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) y Cochrane Library. Los datos referentes a resistencia enzimática a los carbapenémicos se evaluaron mediante metaanálisis según el efecto aleatorio. Resultados: Se seleccionaron 21 artículos según criterios de inclusión y exclusión que evaluaron 1.096 CRAB. La mayoría de los estudios se llevaron a cabo en las regiones sur (33,3%) y sureste (23,8 %) de Brasil (33,3 %) y en los años 2016 y 2018. Según los metaanálisis, la carbapenemasa tipo OXA fue el principal mecanismo implicado en la baja susceptibilidad a los carbapenémicos en CRAB (98 %; IC 95 %: 0,91; 0,99; I² = 95 %), con bla OXA-23-like (91 %; 95 % CI: 0,76; 0,97; I² = 97 %) o bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0,15; 0,99 ; I² = 98 %) genes, seguida de metalo-ß-lactamasas (MBL ) (12 %; IC95 %: 0,09; 0,15; I² = 99 %) y Klebsiella pneumoniae carbapenemase (KPC) (6 %; IC95 %: 0,04; 0,08; I² = 87 %). Conclusión: Los estudios incluidos mostraron que la susceptibilidad a la colistina (99 %) y tigeciclina (93 %) sigue siendo alta y no se ve afectada por la resistencia a los carbapenémicos.

Introdução: As infecções causadas por Acinetobacter baumannii resistente aos carbapenémicos (CRAB) são um problema de saúde devido às limitadas opções terapêuticas disponíveis. Este estudo foi realizado para avaliar os principais mecanismos de resistência aos carbapenêmicos em CRAB nos últimos 10 anos no Brasil e descrever o perfil de susceptibilidade à tigeciclina e às polimixinas nesses isolados. Material e métodos: Foi conduzida uma revisão sistemática segundo o Prisma nas bases de dados PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) e Biblioteca Cochrane. Os dados relativos à resistência enzimática aos carbapenêmicos foram avaliados por meta-análises de acordo com o efeito aleatório. Resultados: Foram selecionados 21 artigos de acordo com os critérios de inclusão e exclusão que avaliaram 1.096 CRAB. A maioria dos estudos foi realizada nas regiões Sul (33,3 %) e Sudeste (23,8 %) do Brasil e nos anos de 2016 e 2018. De acordo com as metanálises, a carbapenemase do tipo OXA foi o principal mecanismo envolvido na baixa susceptibilidade aos carbapenêmicos em CRAB (98 %; 95% IC: 0.91, 0.99; I² = 95 %), com bla OXA-23-like (91 %; 95 %; IC: 0,76; 0,97; I² = 97 %) ou bla OXA -51-like / ISAba1 (84 %; 95 % IC: 0.15, 0.99; I² = 98 %) genes, seguidos por metalo-ß-lactamases (MBL) (12 %, 95 % IC: 0,09, 0,15, I² = 99 %) e Klebsiella pneumoniae carbapenemase (KPC) (6 %, IC 95 %: 0,04; 0,08; I² = 87 %). Conclusão: Os estudos incluídos mostraram que a susceptibilidade à colistina (99 %) e tigeciclina (93 %) permanece alta e não foi afetada pela resistência aos carbapenêmicos.

Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.

Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses.

Epidemiological aspects of the Oropouche virus (Orthobunyavirus) in South America: A systematic review

SUMMARY Introduction: The Oropouche virus (OROV) is an arbovirus that belongs to the genus Orthobunyavirus and family Peribunyaviridae, responsible for causing Oropouche fever (OF) in humans. The clinical diagnosis of is doubtful due to the non-specificity of the symptoms, which can lead to a mistaken diagnosis of other arboviruses. Thus, the survey of epidemiological data on the occurrence of has been a major challenge for public health authorities, especially in of South America. Aim: To determine the general exposure rate of OROV in Brazil and other countries in South America by a systematic review. An article search was carried out in the Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) and Virtual Health Library (VHL) databases. Results: 18 studies were selected as eligible to compose this review on epidemiological aspects of OROV. The studies were published from 1989 to 2020. Most studies were carried out in Brazil (12/18; 66.66%) and Peru (5/18; 27.77%), only one study collected samples from Peru, Ecuador, Bolivia and Paraguay. The test for the OROV was realized mainly by serological analysis. Of the 8005 samples analyzed, 1570 tested positive for the presence of OROV thus accounting a general exposure rate in South America of 19.61%. Brazil was responsible for more than half of the cases of OROV identified in South America (855/1570; 54.46%), however Peru has the highest rate of exposure to the virus (23.43% of frequency in Peru vs. 16.77% of frequency in Brazil). Conclusion: OROV stands out as an important public health problem in Amazonian countries in South America.

Introdução: o virus Oropouche (OROV) é um arbovírus pertencente ao gênero Orthobunyavirus e família Peribunyaviridae, responsável por causar a febre Oropouche (FO) em humanos. O diagnóstico clínico da FO é duvidoso devido à não especificidade dos sintomas, o que pode levar a um diagnóstico equivocado de outras arboviroses. Assim, o levantamento de dados epidemiológicos sobre a ocorrência de FO tem sido um grande desafio para as autoridades de saúde pública, principalmente na América do Sul. Objetivo: determinar a taxa geral de exposição de OROV no Brasil e em outros países da América do Sul por meio de uma revisão sistemática. Foi realizada busca de artigos nas bases de dados Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) e Virtual Health Library (BVS). Resultados: 18 estudos foram selecionados como elegíveis para compor esta revisão sobre aspectos epidemiológicos da OROV. Os estudos foram publicados de 1989 a 2020. A maioria dos estudos foi realizada no Brasil (18/12; 66,66%) e Peru (18/5; 27,77%), apenas um estudo coletou amostras do Peru, Equador, Bolívia e Paraguai. O teste para o OROV foi realizado principalmente por análise sorológica. Das 8005 amostras analisadas, 1570 testaram positivo para a presença de OROV, representando assim uma taxa de exposição geral na América do Sul de 19,61%. O Brasil foi responsável por mais da metade dos casos de OROV identificados na América do Sul (855/1570; 54,46%), porém o Peru tem a maior taxa de exposição ao vírus (23,43% de frequência no Peru vs. 16,77% de frequência em Brasil). Conclusão: OROV destaca-se como um importante problema de saúde pública nos países amazônicos da América do Sul.

Introducción: el virus Oropouche (OROV) es un arbovirus que pertenece al género Orthobunyavirus y familia Peribunyaviridae, responsable de causar la fiebre de oropouche (FO) en humanos. El diagnóstico clínico de FO es dudoso debido a la inespecificidad de los síntomas, lo que puede conducir a un diagnóstico erróneo de otros arbovirus. Por lo tanto, el levantamiento de datos epidemiológicos sobre la ocurrencia de FO ha sido un gran desafío para las autoridades de salud pública, especialmente en el sur de América del Sur. Objetivo: determinar la tasa de exposición general de OROV en Brasil y otros países de América del Sur mediante una revisión sistemática. Se realizó una búsqueda de artículos en las bases de datos Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) y Virtual Health Library (BVS). Resultados: 18 estudios fueron seleccionados como elegibles para esta revisión sobre aspectos epidemiológicos de OROV. Los estudios se publicaron entre 1989 y 2020. La mayoría de los estudios se realizaron en Brasil (12/18; 66,66 %) y Perú (5/18; 27,77 %), solo un estudio recolectó muestras de Perú, Ecuador, Bolivia y Paraguay. La prueba para el OROV se realizó principalmente por análisis serológico. De las 8005 muestras analizadas, 1570 dieron positivo a la presencia de OROV, lo que representa una tasa de exposición general en América del Sur del 19,61 %. Brasil fue responsable de más de la mitad de los casos de OROV identificados en América del Sur (855/1570; 54,46 %), sin embargo, Perú tiene la tasa más alta de exposición al virus (23,43 % de frecuencia en Perú vs. 16,77 % de frecuencia en Brasil). Conclusión: OROV se destaca como un importante problema de salud pública en los países amazónicos de América del Sur.

Profile and costs of dengue hospitalizations in Southeast Pará from the SUS perspective (2000-2015) / Perfil e custos das internações por dengue no Sudeste do Pará na perspectiva do SUS (2000-2015) / Perfil y costos de las hospitalizaciones por dengue en el Sudeste de Pará en la perspectiva del SUS (2000-2015)

Background and objectives: Considering the little evidence associated with dengue hospitalizations, their public expenditures in Southeast Pará and its relevance to the public health in Brazil, this study aims to demonstrate the records of hospitalizations and expenses associated with this arbovirus between 2000 and 2015 from the perspective of the Unified Health System (SUS). Methods: This is a descriptive research that sought to assess the records and expenses (USD) of hospitalization caused by dengue (SUS code: 74500457, 74300440, 0303010010) and severe dengue (SUS code: 74300628, 74500627, 0303010029), as well as their associated deaths (CID: A90 and A91), respectively, from the SIH/SUS and SIM/SUS from 2000 to 2015 for all 39 municipalities in the southeast of Pará. Results: A total of 1206 deaths, 22,860 individuals with dengue and 306 with severe dengue underwent services in the SUS between 2000 and 2015, representing 23,166 hospitalizations (23,613: dengue and 313: severe dengue), in which Bom Jesus do Tocantins and Goianésia do Pará represent the municipalities with the highest number of hospitalizations associated with dengue. Conclusion: It is possible to verify the relevance of continuing efforts to combat and fight dengue in southeastern Pará. It reinforces the need to conduct studies that contribute to a better understanding of the distribution of hospitalizations and deaths in the different municipalities of the state of Pará, as well as reflections on the epidemiological and economic scenario for the implementation of a rational and efficient decision-making process.(AU)

Justificativa e objetivos: Considerando as poucas evidências associadas às internações por dengue, seus gastos públicos no Sudeste do Pará e sua relevância para a saúde pública no Brasil, este estudo tem como objetivo demonstrar os registros de internações e gastos associados a esta arbovirose entre 2000 e 2015 a partir da perspectiva do Sistema Único de Saúde (SUS). Métodos: Trata-se de uma pesquisa descritiva que buscou avaliar os registros e gastos (USD) de internação por dengue (código SUS: 74500457, 74300440, 0303010010) e dengue grave (código SUS: 74300628, 74500627, 0303010029), bem como seus óbitos associados (CID: A90 e A91), respectivamente, do SIH/SUS e SIM/SUS de 2000 a 2015 para todos os 39 municípios do sudeste paraense. Resultados: Um total de 1.206 óbitos, 22.860 indivíduos com dengue e 306 com dengue grave foram atendidos no SUS entre 2000 e 2015, representando 23.166 internações (23.613: dengue e 313: dengue grave), nas quais Bom Jesus do Tocantins e Goianésia do O Pará representa os municípios com maior número de internações associadas à dengue. Conclusão: É possível verificar a relevância da continuidade dos esforços de combate e combate à dengue no sudeste paraense. Reforça a necessidade da realização de estudos que contribuam para um melhor entendimento da distribuição das internações e óbitos nos diferentes municípios do estado do Pará, bem como reflexões sobre o cenário epidemiológico e econômico para a implementação de um processo decisório racional e eficiente. Fazendo processo.(AU)

Justificación y objetivos: Considerando la poca evidencia asociada a las hospitalizaciones por dengue, sus gastos públicos en el Sudeste de Pará y su relevancia para la salud pública en Brasil, este estudio tiene como objetivo demostrar los registros de hospitalizaciones y gastos asociados a este arbovirus entre 2000 y 2015 a partir de la perspectiva del Sistema Único de Salud (SUS). Métodos: Se trata de una investigación descriptiva que buscó evaluar los registros y gastos (USD) de hospitalización por dengue (código SUS: 74500457, 74300440, 0303010010) y dengue grave (código SUS: 74300628, 74500627, 0303010029), así como sus muertes asociadas (CID: A90 y A91), respectivamente, del SIH/SUS y SIM/SUS de 2000 a 2015 para los 39 municipios del sureste de Pará. Resultados: Un total de 1206 muertes, 22.860 personas con dengue y 306 con dengue grave fueron atendidos en el SUS entre 2000 y 2015, lo que representa 23.166 hospitalizaciones (23.613: dengue y 313: dengue grave), en las que Bom Jesus do Tocantins y Goianésia hacen Pará representan los municipios con mayor número de hospitalizaciones asociadas al dengue. Conclusión: Es posible verificar la relevancia de continuar los esfuerzos para combatir y luchar contra el dengue en el sureste de Pará. Refuerza la necesidad de realizar estudios que contribuyan a una mejor comprensión de la distribución de hospitalizaciones y muertes en los diferentes municipios del estado de Pará, así como reflexiones sobre el escenario epidemiológico y económico para la implementación de una decisión racional y eficiente. proceso de fabricación.(AU)

Antifungal effect of hydroethanolic extract of Fridericia chica (Bonpl.) L. G. Lohmann leaves and its therapeutic use in a vulvovaginal candidosis model.

Vulvovaginal candidosis (VVC) is one of the most frequent causes of gynecological consultations. Therefore, the development of new antifungal therapies against VVC is relevant. In this context, the leaves of Fridericia chica (Bonpl.) L. G. Lohmann are considered a therapeutic alternative since they are traditionally used in VVC therapy. However, no scientific evidence has supported this use against fungal vaginal infections. Then, we aimed to characterize the antifungal effect of a hydroethanolic extract of F. chica leaves (HEFc) and evaluate the therapeutic potential of this extract in a VVC model. HEFc inhibited the growth of C. albicans (256-1,204 µg/mL) and C. krusei (512 µg/mL) in vitro. HEFc inhibited yeast-to-hypha transition in C. albicans and has a low ability to induce resistance in this species. Intravaginal use of the HEFc at 50 mg/mL causes mycological cure in animals with VVC after 6 days of treatment, similar to the effect observed for the commercial antifungal nystatin. These results support the traditional use of F. chica leaves as a topical therapeutic option to treat VVC.

Netzahualcoyonol from Salacia multiflora (Lam.) DC. (Celastraceae) roots as a bioactive compound against gram-positive pathogens.

The expression of virulence factors, such as biofilm formation, in association with the acquisition of resistance to multiple drugs, has evidenced the need for new and effective antimicrobial agents against Staphylococcus aureus. The evaluation of the pharmacological properties of plant-derived compounds is a promising alternative to the development of new antimicrobials. In this study, we aimed to evaluate the antibacterial, antibiofilm, and the synergistic and cytotoxic effects of netzahualcoyonol isolated from Salacia multiflora (Lam.) DC. roots. Netzahualcoyonol presented bacteriostatic (1.56-25.0 µg/mL) and bactericidal (25.0-400.0 µg/mL) effects against Gram-positive bacteria, disrupted the biofilm of S. aureus, and presented a synergistic effect after its combination with ß-lactams and aminoglycosides. The low cytotoxicity of netzahualcoyonol (Selectivity Index (SI) for S. aureus (2.56), S. saprophyticus (20.56), and Bacillus subtilis (1.28)) suggests a good security profile. Taken together, these results show that netzahualcoyonol is promising for the development of a new effective antibacterial agent.

Antibacterial, anti-biofilm, and anti-adhesive activities of melittin, a honeybee venom-derived peptide, against quinolone-resistant uropathogenic Escherichia coli (UPEC).

Here, we demonstrated the in vitro and in vivo antibacterial and anti-biofilm activities of melittin, a peptide derived from honeybee venom, against uropathogenic Escherichia coli (UPEC) resistant to quinolones. The minimum inhibitory concentration (MIC) of melittin varied from 0.5 to 8 µM. The bactericidal effect was considered rapid and potent (ranging from 3.0 to 6.0 h after incubation) against a quinolone-resistant and Extended Spectrum Beta-lactamase (ESBL)-producing UPEC strain. Prior exposure to melittin did not reduce the MIC of the quinolones tested, but it decreased the MIC of ceftizoxime by 8-fold due to its ability to form pores in the membrane. Furthermore, melittin disrupted mature biofilms (39.58% at 32 µM) and inhibited the adhesion of this uropathogen to the surfaces of urethral catheter. These results show that melittin is a promising molecule that can be incorporated into invasive urethral medical devices to prevent urinary infections caused by multidrug-resistant UPECs.

Effect of honey and propolis, compared to acyclovir, against Herpes Simplex Virus (HSV)-induced lesions: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results. AIM OF THE STUDY: Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes. MATERIALS AND METHODS: The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library. RESULTS: The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to -0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to -0.42; p = 0.18). CONCLUSIONS: Overall, these results confirm the use of honey and propolis as potent antiherpetic agents.

NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Occurrence of extended-spectrum beta-lactamase (ESBL) and carbapenemases among ampicillin-resistant enterobacteriales recovered from a municipal raw sewage in Minas Gerais, Brazil

SUMMARY Introduction: The capacity of resistance to ß-lactam among enterobacteriales is notable, mainly into water environment. Herein, many species of this family have the ability to carrier and produce ß-lactamases enzymes, such as extended-spectrum ß-lactamases (ESBLs) and carbapenemases. However, contrary to clinical settings, where the distribution of resistant bacteria is well documented, the evidence of resistant pathogens in the domestic sewage has been little explored, especially in Brazil. Thus, we aimed to investigate the occurrence of ESBL and carbapenemases between ampicillin-resistant enterobacteriales recovered from a municipal raw sewage in Minas Gerais, Brazil. Methods: Enterobacteriales were isolated from sewage samples on MacConkey agar supplemented with ampicillin. Species identification was performed by biochemical and morphological methods and the resistance profile determined by the Kirby-Bauer test. The production of ESBL and carbapenemase was investigated in all isolates by phenotypic tests. Results and discussion: A total of 45 species of enterobacteriales resistant to ampicillin were recovered (37 Escherichia coli, four Klebsiella pneumoniae, and one Klebsiella oxytoca, Citrobacter freundii and Pantoea agglomerans). Most isolates showed a high ß-lactam susceptibility profile (14/45, 31.1 %), however E. coli with decreased susceptibility to imipenem was detected (2/37; 2.7 %). ESBL-positive isolates were mostly identified as E. coli (10/45; 22.2 %), but no isolates were positive carbapenemase. Conclusion: Domestic sewage is an important source of ß-lactams resistant determinants in Brazil.

Introdução: a capacidade de resistência aos beta-lactâmicos entre enterobacteriales é notável, principalmente no ambiente aquático. Nessa direção, muitas espécies desta família têm a capacidade de transportar e produzir enzimas ß-lactamases, especialmente a ß-lactamases de espectro estendido (ESBL) e as carbapenemases. Porém, ao contrário do cenário clínico, onde a distribuição de bactérias resistentes é bem documentada, as evidências de patógenos resistentes no esgoto doméstico têm sido pouco exploradas, principalmente no Brasil. Assim, objetivamos investigar a ocorrência de ESBL e carbapenemases entre enterobacteriales resistentes à ampicilina recuperadas de um esgoto bruto municipal em Minas Gerais, Brasil. Métodos: enterobacteriales foram isoladas de amostras de esgoto em ágar MacConkey suplementado com ampicilina. A identificação das espécies foi realizada por métodos bioquímicos e morfológicos e o perfil de resistência determinado pelo teste de Kirby-Bauer. A produção de ESBL e carbapenemase foi investigada em todos os isolados por testes fenotípicos. Resultados e discussão: foram recuperadas 45 isolados de enterobacteriales resistentes à ampicilina (37 Escherichia coli, quatro Klebsiella pneumoniae e uma Klebsiella oxytoca, Citrobacter freundii e Pantoea agglomerans). A maioria dos isolados apresentou um perfil de alta susceptibilidade aos ß-lactâmicos (14/45, 31,1 %), porém E. coli com susceptibilidade diminuída ao imipenem foi detectada (2/37; 2,7 %). Os isolados ESBL-positivos foram identificados principalmente como E. coli (10/45; 22,2 %), mas nenhum isolado foi positivo para a carbapenemase. Conclusão: o esgoto doméstico é uma importante fonte de determinantes de resistência aos ß-lactâmicos no Brasil.

Introducción: la capacidad de resistencia a betalactámicos entre enterobacteriales es notable, principalmente en el medio acuático. En este sentido, muchas especies de esta familia tienen la capacidad de transportar y producir enzimas ß-lactamasas, especialmente ß-lactamasas de espectro extendido (BLEE) y carbapenemasas. Sin embargo, en contraste con el escenario clínico, donde la distribución de bacterias resistentes está bien documentada, la evidencia de patógenos resistentes en las aguas residuales domésticas ha sido poco explorada, especialmente en Brasil. Por lo tanto, nuestro objetivo es investigar la ocurrencia de BLEE y carbapenemasas entre enterobacteriales resistentes a ampicilina recuperadas de un alcantarillado municipal sin tratar en Minas Gerais, Brasil. Métodos: se aislaron enterobacteriales de muestras de aguas residuales en agar MacConkey suplementado con ampicilina. La identificación de las especies se realizó mediante métodos bioquímicos y morfológicos y el perfil de resistencia se determinó mediante la prueba de Kirby-Bauer. La producción de BLEE y carbapenemasa se investigó en todos los aislamientos mediante pruebas fenotípicas. Resultados y discusión: se recuperaron 45 aislamientos de enterobacteriales resistentes a ampicilina (37 Escherichia coli, cuatro Klebsiella pneumoniae y una Klebsiella oxytoca, Citrobacter freundii y Pantoea agglomerans). La mayoría de los aislamientos tenían un perfil de susceptibilidad alto a los (3-lactámicos (14/45, 31,1 %), pero se detectó E. coli con susceptibilidad reducida al imipenem (2/37; 2,7 %). Los aislamientos positivos para BLEE se identificaron principalmente como E. coli (10/45; 22,2 %), pero ningún aislado fue positivo para carbapenemasa. Conclusión: las aguas residuales domésticas son una fuente importante de determinantes de la resistencia a los ß-lactámicos en Brasil.

A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance.

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: Systematic review and meta-analysis of preclinical studies.

Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin-type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin-type flavonols with significantly reduced mortality rate (M-H = 0.19, 95% CI: 0.05 to 0.65, p-value = 0.008) of infected animals and a reduction in the average viral load (IV = -1.93, 95% CI: -3.54 to -0.31, p-value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin-type flavonols is a promising strategy for treating viral-induced lower respiratory tract infections.