RESUMO
Since early 2020, disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, causing millions of infections and deaths worldwide. Despite rapid deployment of effective vaccines, it is apparent that the global community lacks multipronged interventions to combat viral infection and disease. A major limitation is the paucity of antiviral drug options representing diverse molecular scaffolds and mechanisms of action. Here we report the antiviral activities of three distinct marine natural productsâhomofascaplysin A (1), (+)-aureol (2), and bromophycolide A (3)âevidenced by their ability to inhibit SARS-CoV-2 replication at concentrations that are nontoxic toward human airway epithelial cells. These compounds stand as promising candidates for further exploration toward the discovery of novel drug leads against SARS-CoV-2.
Assuntos
Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Células Epiteliais , Humanos , SARS-CoV-2RESUMO
The rise of antibiotic resistance has necessitated a search for new antimicrobials with potent activity against multidrug-resistant gram-negative pathogens, such as carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, a library of botanical extracts generated from plants used to treat infections in traditional medicine was screened for growth inhibition of CRAB. A crude extract of Schinus terebinthifolia leaves exhibited 80% inhibition at 256 µg/mL and underwent bioassay-guided fractionation, leading to the isolation of pentagalloyl glucose (PGG), a bioactive gallotannin. PGG inhibited growth of both CRAB and susceptible A. baumannii (MIC 64-256 µg/mL), and also exhibited activity against Pseudomonas aeruginosa (MIC 16 µg/mL) and Staphylococcus aureus (MIC 64 µg/mL). A mammalian cytotoxicity assay with human keratinocytes (HaCaTs) yielded an IC50 for PGG of 256 µg/mL. Mechanistic experiments revealed iron chelation as a possible mode of action for PGG's activity against CRAB. Passaging assays for resistance did not produce any resistant mutants over a period of 21 days. In conclusion, PGG exhibits antimicrobial activity against CRAB, but due to known pharmacological restrictions in delivery, translation as a therapeutic may be limited to topical applications such as wound rinses and dressings.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Anacardiaceae/química , Antibacterianos/farmacologia , Taninos Hidrolisáveis/farmacologia , Resistência beta-Lactâmica/efeitos dos fármacos , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Carbapenêmicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Correction for 'Recent trends in the structural revision of natural products' by Bhuwan Khatri Chhetri et al., Nat. Prod. Rep., 2018, 35, 514-531.
RESUMO
Covering: 2012 to 2017 This article reviews recent reports on the structural revision of natural products. Through a critical assessment of the original and revised published structures, the article addresses why each structure was targeted for revision, discusses the techniques and key discrepancies that led to the proposal of the revised structure, and offers measures that may have been taken during the original structure determination to prevent error. With the revised structures in hand, weaknesses of original proposals are assessed, providing a better understanding on the logic behind structure determination.
