Clinical and Epidemiological Assessment of Children and Adolescents Hospitalized with SARS-CoV-2 in the Pre-Amazon Region.

INTRODUCTION: SARS-CoV-2 infection usually presents similarly to other respiratory viral pathogens. Children and adolescents do not present as a group that is highly affected by the disease, having low infection rates. However, limited publications are associated with the findings of pneumonia in pediatric patients with COVID-19. OBJECTIVE: To analyze the clinical and epidemiological aspects of children and adolescents hospitalized with SARS-CoV-2 in a pre-Amazon region. METHODS: A retrospective study, carried out in four public hospitals in São Luís, Brazil where medical records of children and adolescents aged from 0 to 13 years, of both sexes, with clinical diagnosis of community-acquired pneumonia were evaluated from March 2020 to March 2021. RESULTS: Almost 40.0% of children were aged between 1 year and 5 years. Of the 128 children who had SARS-CoV-2, 3 are of indigenous ethnicity. Additionally, 78.6% of the children had fever and there was no significant difference between COVID-19 patients and those of other respiratory viruses. Eighteen patients had chronic neurological disease, which is the most common comorbidity observed in patients with coronavirus infection. Ground glass opacity attenuation was observed in 24.8% of children and adolescents with COVID-19. Anemia and increased inflammatory response markers were related to SARS-CoV-2 infection. More than 90.0% of patients admitted to hospital, regardless of etiology, were treated with antibiotics. Eighteen patients died. Pediatric multisystem inflammatory syndrome (PMIS) was diagnosed in 17 patients. CONCLUSIONS: SARS-CoV-2 in children and adolescents is mild, but the condition of patients with PMIS is more serious, with an increase in inflammatory biomarkers which can lead to death. Therefore, rapid diagnosis and differentiation of agents causing respiratory diseases are necessary for better therapeutic decision making, since the results of this study make us question the excessive use of antibiotics without meeting well-defined clinical-epidemiological criteria.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

Dioclea violacea lectin increases the effect of neomycin against multidrug-resistant strains and promotes the purification of the antibiotic in immobilized lectin column.

DVL is a Man/Glc-binding lectin from Dioclea violacea seeds that has the ability to interact with the antibiotic gentamicin. The present work aimed to evaluate whether the DVL has the ability to interact with neomycin via CRD and to examine the ability of this lectin to modulate the antibiotic effect of neomycin against multidrug-resistant strains (MDR). The hemagglutinating activity test revealed that neomycin inhibited the hemagglutinating activity of DVL with a minimum inhibitory concentration of 50 mM, indicating that the antibiotic interacts with DVL via the carbohydrate recognition domain (CRD). DVL immobilized on cyanogen bromide-activated Sepharose® 4B bound 41 % of the total neomycin applied to the column, indicating that the DVL-neomycin interaction is efficient for purification processes. Furthermore, the minimum inhibitory concentrations (MIC) obtained for DVL against all strains studied were not clinically relevant. However, when DVL was combined with neomycin, a significant increase in antibiotic activity was observed against S. aureus and P. aeruginosa. These results demonstrate the first report of lectin-neomycin interaction, indicating that immobilized DVL has the potential to isolate neomycin by affinity chromatography. Moreover, DVL increased the antibiotic activity of neomycin against MDR, suggesting that it is a potent adjuvant in the treatment of infectious diseases.

Nickel (II) chloride schiff base complex: Synthesis, characterization, toxicity, antibacterial and leishmanicidal activity.

The use of schiff base complex against microbial agentes a has recently received more attention as a strategy to combat infections caused by multidrug-resistant bacteria and leishmania. This study aimed to evaluate the toxicity, antibacterial and leishmanicidal activities of the nickel (II) chloride schiff base complex ([Ni(L2)] against Leishmania amazonensis promastigote, multi-resistant bacterial strains and evaluate to modulate antibiotic activity against multi-resistant bacterial. The schiff base complex was characterized by the techniques of elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-vis absorption spectroscopy and thermal analysis (TGA/DTG/DSC). The [Ni(L2)] complex presented moderate toxicity in saline artemia (LC50 = 150.8 µg/mL). In leishmanicidal assay, the NiL2 complex showed values of IC50 of (6.079 µg/mL ± 0.05656 at the 24 h), (0.854 µg/mL ± 0.02474, 48 h) and (1.076 µg/mL ± 0.04039, 72 h). In antibacterial assay, the [Ni(L2)] complex presented significant inhibited the bacterial growth of P. aeruginosa (MIC = 256 µg/mL). However, [Ni(L2)] complex did not present clinically relevant minimum inhibitory concentration (MIC ≥1024 µg/mL) against S. aureus and E. coli. The combination of [Ni(L2)] complex and antibacterial drugs resulted in the increased antibiotic activity of gentamicin and amikacin against S. aureus and E.coli multi-resistant strains. Thus, our results showed that [Ni(L2)] complex is a promising molecule for the development of new therapies associated with aminoglycoside antibiotics and in disease control related to resistant bacteria and leishmaniasis.

Enhanced antibacterial activity of the gentamicin against multidrug-resistant strains when complexed with Canavalia ensiformis lectin.

The lectins are carbohydrate-binding proteins that are highly specific to sugar groups associated to other molecules. In addition to interacting with carbohydrates, a number of studies have reported the ability of these proteins to modulate the activity of several antibiotics against multidrug-resistant (MDR) strains. In this study, we report the enhanced antibacterial activity of the gentamicin against MDR strains when complexed with a lectin from Canavalia ensiformis seeds (ConA). Hemagglutination activity test and intrinsic fluorescence spectroscopy revealed that the gentamicin can interact with ConA most likely via the carbohydrate recognition domain (CRD) with binding constant (Kb) value estimated of (0.44 ± 0.04) x 104 M-1. Furthermore, the minimum inhibitory concentrations (MIC) obtained for ConA against all strains studied were not clinically relevant (MIC ≥ 1024 µg/mL). However, when ConA was combined with gentamicin, a significant increase in antibiotic activity was observed against Staphylococcus aureus and Escherichia coli. The present study showed that ConA has an affinity for gentamicin and modulates its activity against MDR strains. These results indicate that ConA improves gentamicin performance and is a promising candidate for structure/function analyses.

The Galactose-Binding Lectin Isolated from Vatairea macrocarpa Seeds Enhances the Effect of Antibiotics Against Staphylococcus aureus-Resistant Strain.

The use of natural products together with standard antimicrobial drugs has recently received more attention as a strategy to combat infectious diseases caused by multidrug-resistant (MDR) microorganisms. This study aimed to evaluate the capacity of a galactose-binding lectin from Vatairea macrocarpa seeds (VML) to modulate antibiotic activity against standard and MDR Staphylococcus aureus and Escherichia coli bacterial strains. The minimum inhibitory concentration (MIC) obtained for VML against all strains was not clinically relevant (MIC ≥ 1024 µg/mL). However, when VML was combined with the antibacterial drugs gentamicin, norfloxacin and penicillin, a significant increase in antibiotic activity was observed against S. aureus, whereas the combination of VML and norfloxacin presented decreased and, hence, antagonistic antibiotic activity against E. coli. By its inhibition of hemagglutinating activity, gentamicin (MIC = 50 mM) revealed its interaction with the carbohydrate-binding site (CBS) of VML. Using molecular docking, it was found that gentamicin interacts with residues that constitute the CBS of VML with a score of - 120.79 MDS. It is this interaction between the antibiotic and the lectin's CBS that may be responsible for the enhanced activity of gentamicin in S. aureus. Thus, our results suggest that the VML can be an effective modulating agent against S. aureus. This is the first study to report the effect of lectins as modulators of bacterial sensitivity, and as such, the outcome of this study could lay the groundwork for future research involving the use of lectins and conventional antibiotics against such infectious diseases such as community-acquired methicillin-resistant S. aureus (MRSA).

Dioclea violacea lectin modulates the gentamicin activity against multi-resistant strains and induces nefroprotection during antibiotic exposure.

Gentamicin is an aminoglycoside antibiotic used to treat infections of various origins. In the last few decades, the constant use of gentamicin has resulted in increased bacterial resistance and nephrotoxicity in some cases. In this study, we examined the ability of Dioclea violacea lectin (DVL) in modulate the antimicrobial activity of gentamicin and reduce the nephrotoxicity induced by this drug. The minimum inhibitory concentration (MIC) obtained for DVL against all strains studied was not clinically relevant (MIC ≥ 1024 µg/mL). However, when DVL was combined with gentamicin, a significant increase in antibiotic action was observed against Staphylococcus aureus and Escherichia coli. DVL also reduced antibiotic tolerance in S. aureus during 10 days of continuous treatment. In addition, DVL presented a nephroprotective effect, reducing sodium excretion, N-Gal expression and urinary protein, that are important markers of glomerular and tubular injuries. Taken together, studies of inhibition of hemagglutinating activity, fluorescence spectroscopy and molecular docking revealed that gentamicin can interact with DVL via the carbohydrate recognition domain (CRD), suggesting that the results obtained in this study may be directly related to the interaction of DVL-gentamicin and with the ability of the lectin to interact with glycans present in the cells of the peritoneum.

Parkia platycephala lectin enhances the antibiotic activity against multi-resistant bacterial strains and inhibits the development of Haemonchus contortus.

Lectins have been studied in the past few years as an alternative to inhibit the development of pathogenic bacteria and gastrointestinal nematodes of small ruminants. The development of new antibacterial and anthelmintic compounds is necessary owing to the increase in drug resistance among important pathogens. Therefore, this study aimed to evaluate the capacity of a glucose/mannose-binding lectin from Parkia platycephala seeds (PPL) to inhibit the development of Haemonchus contortus and to modulate antibiotic activity against multi-resistant bacterial strains, thereby confirming its efficacy when used in combination with gentamicin. PPL at the concentration of 1.2 mg/mL did not show inhibitory activity on H. contortus in the egg hatch test or the exsheathment assay. However, it did show significant inhibition of H. contortus larval development with an IC50 of 0.31 mg/mL. The minimum inhibitory concentration (MIC) obtained for PPL against all tested bacterial strains was not clinically relevant (MIC ≥ 1024 µg/mL). However, when PPL was combined with gentamicin, a significant increase in antibiotic activity was observed against S. aureus and E.coli multi-resistant strains. The inhibition of hemagglutinating activity by gentamicin (MIC = 50 mM) revealed that it may be interacting with the carbohydrate-binding site of PPL. It is this interaction between the antibiotic and lectin carbohydrate-binding site that may be responsible for the enhanced activity of gentamicin against multi-resistant strains. It can be concluded that PPL showed selective anthelmintic effect, inhibiting the development of H. contortus larvae and that it increased the effect of the antibiotic gentamicin against multi-resistant bacterial strains, thus constituting a potential therapeutic resource against resistant bacterial strains and H. contortus.

Purification and biophysical characterization of a mannose/N-acetyl-d-glucosamine-specific lectin from Machaerium acutifolium and its effect on inhibition of orofacial pain via TRPV1 receptor.

A new mannose/N-acetyl-dglucosamine-specific lectin, named MaL, was purified from seeds of Machaerium acutifolium by precipitation with ammonium sulfate, followed by affinity and ion-exchange chromatography. MaL haemagglutinates either native rabbit erythrocytes or those treated with proteolytic enzymes. MaL is highly stable by the ability to maintain its haemagglutinating activity after exposure to temperatures up to 50 °C. The lectin haemagglutinating activity was optimum between pH 6.0 and 7.0 and inhibited after incubation with d-mannose and N-acetyl-d-glucosamine and α-methyl-d-mannopyranoside. MaL is a glycoprotein with relative molecular mass of 29 kDa (α-chain), 13 kDa (ß-chain) and 8 kDa (γ-chain) with secondary structure composed of 3% α-helix, 44% ß-sheet, 21% ß-turn, and 32% coil. The orofacial antinociceptive activity of the lectin was also evaluated. MaL (0.03 mg mL-1) reduced orofacial nociception induced by capsaicin, an effect that occurred via carbohydrate recognition domain interaction, suggesting an interaction of MaL with the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor. Our results confirm the potential pharmacological relevance of MaL as an inhibitor of acute orofacial mediated by TRPV1.

Structural analysis and anthelmintic activity of Canavalia brasiliensis lectin reveal molecular correlation between the carbohydrate recognition domain and glycans of Haemonchus contortus.

Haemonchus contortus is one of the most economically important parasites infecting small ruminants worldwide. This nematode has shown a great ability to develop resistance to anthelmintic drugs, calling for the development of alternative control approaches. Because lectins recognize and bind to specific carbohydrates and glycan structures present in parasites, they can be considered as an alternative to develop new antiparasitic drugs. Accordingly, this work aimed to investigate the anthelmintic effect of Canavalia brasiliensis (ConBr) lectin against H. contortus and to evaluate a possible interaction of ConBr with glycans of this parasite by molecular docking. ConBr showed significant inhibition of H. contortus larval development with an IC50 of 0.26 mg mL-1. Molecular docking assays revealed that glycans containing the core trimannoside [Man(α1-3)Man(α1-6)Man] of H. contortus interact in the carbohydrate recognition domain of ConBr with an interaction value of MDS = -248.77. Our findings suggest that the inhibition of H. contortus larval development is directly related to the recognition of the core trimannoside present in the glycans of these parasites. This work is the first to report on the structure-function relationships of the anthelmintic activity of plant lectins.