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Multidrug efflux systems of the resistance‐nodulation‐cell division family play a crucial role in resistance of Pseudomonas aeruginosa to a large variety of antibiotics. Here, we investigated the role of clinically relevant efflux pumps MexAB−OprM, MexCD−OprJ, and MexXY−OprM in resistance against different cationic antimicrobial peptides (AMPs). Our results indicate that a knock‐out in efflux pump MexXY‐OprM increased susceptibility to some AMPs by two‐ to eightfold. Our data suggest a contribution of MexXY‐OprM in resistance to certain AMPs in P. aeruginosa, which should be considered in the future development of new and highly active antimicrobial peptides to fight multidrug resistant infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Objectives: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti‐epileptic treatment in this group of patients. Methods: A systematic review and meta‐analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study. Results: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta‐analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51‐0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to anti‐epileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year. Significance: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti‐epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients. [ABSTRACT FROM AUTHOR]

The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. [ABSTRACT FROM AUTHOR]