Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current pandemic of coronavirus disease 2019 (COVID-19) that has inflicted the loss of thousands of lives worldwide. The coronavirus surface spike (S) glycoprotein is a class I fusion with a S1 domain which is attached to the human angiotensin converting enzyme 2 (ACE2) receptor, and a S2 domain which enables fusion with the host cell membrane and internalization of the virus. Curcumin has been suggested as a potential drug to control inflammation and as a potential inhibitor of S protein, but its therapeutic effects are hampered by poor bioavailability. We performed a molecular docking and dynamic study using 94 curcumin analogues designed to have improved metabolic stability against the SARS-CoV-2 spike protein and compared their affinity with curcumin and other potential inhibitors. The docking analysis suggested that the S2 domain is the main target of these compounds and compound 2606 displayed a higher binding affinity (-9.6 kcal mol-1) than curcumin (-6.8 kcal mol-1) and the Food and Drug Administration (FDA) approved drug hydroxychloroquine (-6.3 kcal mol-1). Further additional validation in vitro and in vivo of these compounds against SARS-CoV-2 may provide insights into the development of a drug that prevents virus entry into host cells.

Anemopaegma arvense pertence à família Bignoniaceae, sendo conhecida popularmente como Catuaba. Para avaliação de sua atividade citotóxica e antimicrobiana, a fração cromatográfica F3 e os flavonoides 1 (quercetina 3-O-α-L-ramnopiranosil-(1→6)-β-D-glucopiranosídeo) (rutina) e flavonoide 2 (quercetina 3-O-α-L-ramnopiranosil-(1→6)-β-D-galactopiranosídeo) foram isolados das folhas de A. arvense. A fração 3 e os flavonoides não apresentaram atividade antibacteriana. Nenhuma atividade citotóxica foi observada para a fração F3 e para os flavonoides, quando avaliados contra as células tumorais em teste. Entretanto, e considerando a atividade antifúngica, o flavonóide 1 apresentou valor de concentração inibitória mínima (CIM) de 0,5 mg/mL, enquanto o flavonóide 2, CIM de 0,25 mg/mL contra as cepas selvagem e mutante de Trichophyton rubrum, demonstrando, pela primeira vez, que os flavonoides isolados possuem atividade antifúngica, o que valida a mesma atividade para A. arvense.

Anemopaegma arvense (Vell) Stellf. ex de Souza belongs to the family Bignoniaceae, and is popularly known as catuaba. To evaluate the cytotoxic and antimicrobial activity of A. arvense, fraction F3 and flavonoids 1 (quercetin 3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside) (rutin) and flavonoid 2 (quercetin 3-O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside) were isolated from the leaves of this plant. Fraction F3 and flavonoids 1 and 2 exhibited no antibacterial activity. Furthermore, no cytotoxic activity of fraction 3 or flavonoids 1 and 2 was observed against the tumor cells tested. However, analysis of the antifungal activity of flavonoids 1 and 2 revealed minimum inhibitory concentrations of 0.5 and 0.25 mg/mL, respectively, against the Trichophyton rubrum strains tested (wild type and mutant). This study demonstrates for the first time the antifungal activity of isolated flavonoids, validating the same activity for A. arvense.

Leifsonia xyli subsp xyli (Lxx) is the etiological agent of ratoon-stunting disease (RSD), one of the most important diseases that affects productivity of sugarcane crops. The lack of defined external symptoms in most plants is a challenge for the diagnosis of RSD facilitating its spread in production fields. In this study a Taqman® real-time polymerase chain reaction (qPCR) assay was developed for detection of the bacteria in different tissues of the plants and compared to conventional PCR and nested-PCR assays. The bacterial DNA was amplified by the nested-PCR and qPCR assays, indicating that conventional PCR lacks sufficient sensitivity to be used as a diagnostic tool for RSD. On the other hand, qPCR is more advantageous than nested-PCR for processing large amounts of samples since it does not need post processing steps for visualization of results and the level of bacterial infection can be quantified. Therefore by improving the diagnosis of RSD in field plants, it can be applied to monitor losses caused by the disease, as a tool to monitor the efficacy of sanitation procedures and in the development of new sanitizers for Lxx.

Cancer has become a major public health problem worldwide and the number of deaths due to this disease is increasing almost exponentially. In the constant search for new treatments, natural products of plant origin have provided a variety of new compounds to be explored as antitumor agents. Tabernaemontana catharinensis is a medicinal plant that produces alkaloids with expressive antitumor activity, such as heyneanine, coronaridine and voacangine. The aim of present study was firstly to screen the cytotoxic activity of the indole alkaloids heyneanine, coronaridine and voacangine against HeLa (human cervix tumor), 3T3 (normal mouse embryo fibroblasts), Hep-2 (human laryngeal epithelial carcinoma) and B-16 (murine skin) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); and secondly to analyze the apoptotic activity, cell membrane damage and genotoxicity of the compound that showed the best cytotoxic activity against the tumor cell lines tested. Coronaridine was the one that exhibited greater cytotoxic activity in the laryngeal carcinoma cell line Hep-2 (IC50 = 54.47 µg/mL) than the other alkaloids tested (voacangine IC50 = 159.33 µg/mL, and heyneanine IC50 = 689.45 µg/mL). Coronaridine induced apoptosis in cell lines 3T3 and Hep-2, even at high concentrations. The evaluation of genotoxicity by comet assay showed further that coronaridine caused minimal DNA damage in the Hep-2 tumor cell line, and the LDH test showed that it did not affect the plasma membrane. These results suggest that further investigation of coronaridine as an antitumor agent has merit.

INTRODUÇÃO: A fibromialgia é uma síndrome reumática caracterizada por dor difusa e crônica associada a fadiga, insônia, ansiedade, depressão, perda de memória e tontura. Embora os mecanismos fisiológicos que controlam a fibromialgia não tenham sido estabelecidos, fatores neuroendócrinos, genéticos ou moleculares podem estar envolvidos. OBJETIVO: O objetivo do presente estudo foi caracterizar os polimorfismos dos genes do receptor de serotonina (5-HT2A) e da catecolO-metiltransferase (COMT) em pacientes brasileiros com fibromialgia, a fim de avaliar sua participação na etiologia da doença. MATERIAL E MÉTODOS: O DNA genômico extraído de 102 amostras de sangue (51 pacientes, 51 controles) foi usado para a caracterização molecular dos polimorfismos dos genes 5-HT2A e COMT, por meio de PCR-RFLP. RESULTADOS: A análise molecular dos polimorfismos do gene 5-HT2A demonstrou frequências de 25,49% C/C, 49,02% T/C e 25,49% T/T, nos pacientes com fibromialgia, e 17,65% C/C, 62,74% T/C e 19,61% T/T, no grupo controle, não apresentando diferença significativa entre o grupo de pacientes e o grupo controle. Os polimorfismos do gene da COMT em pacientes com fibromialgia apresentaram uma frequência de 17,65% e 45,10% para os genótipos H/H e L/H, respectivamente. No grupo controle, as frequências foram de 29,42%, para H/H, e 60,78%, para L/H, sem diferença significativa entre ambos os grupos. Entretanto, houve diferença significativa na frequência do genótipo L/L em pacientes (37,25%) e controles (9,8%), o que permitiu a diferenciação entre os dois grupos. CONCLUSÃO: A frequência do genótipo L/L foi maior nos pacientes com fibromialgia. Apesar de a fibromialgia envolver uma situação poligênica e fatores ambientais, o estudo molecular do SNP rs4680 do gene da COMT pode auxiliar a identificação de indivíduos suscetíveis.

INTRODUCTION: Fibromyalgia is a rheumatic syndrome characterized by diffuse and chronic pain associated with fatigue, sleep disorders, anxiety, depression, memory loss, and dizziness. Although the physiological mechanisms that control fibromyalgia have not been precisely established, neuroendocrine, genetic or molecular factors may be involved in fibromyalgia. OBJECTIVE: The aim of the present study was to characterize serotonin receptor (5-HT2A) and catecholO-methyltransferase (COMT) gene polymorphisms in Brazilian patients with fibromyalgia and to evaluate the participation of these polymorphisms in the etiology of the disease. MATERIAL AND METHODS: Genomic DNA extracted from 102 blood samples (51 patients, 51 controls) was used for molecular characterization of the 5-HT2A and COMT gene polymorphisms by PCR-RFLP. RESULTS: Analysis of the 5-HT2A polymorphism revealed a frequency of 25.49% C/C, 49.02% T/C and 25.49% T/T in patients, and of 17.65% C/C, 62.74% T/C and 19.61% T/T in the control group, with no differences between the two groups.Analysis of the COMT polymorphism in patients showed a frequency of 17.65% and 45.10% for genotypes H/H and L/H, respectively. In the control group the frequency was 29.42% for H/H and 60.78% for L/H, also with no differences between the two groups. However, there was a significant difference in the frequency of the L/L genotype between patients (37.25%) and controls (9.8%), which permitted differentiation between the two groups. CONCLUSION: The L/L genotype was more frequent among fibromyalgia patients. Though considering a polygenic situation and environmental factors, the molecular study of the rs4680 SNP of the COMT gene may be helpful to the identification of susceptible individuals.