Lessons learnt from broad-spectrum coronavirus antiviral drug discovery DOI

Andrew A. Bolinger,

Jun Li, Xuping Xie

et al.

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: 19(9), P. 1023 - 1041

Published: July 30, 2024

Introduction Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East (MERS-CoV), and the most recent SARS-CoV-2 responsible for COVID-19 pandemic, pose significant threats to human populations over past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic distress syndromes (ARDS), resulting in high morbidity mortality.

Language: Английский

Antibiofilm Activity of Sundew Species against Multidrug-Resistant Escherichia coli Strains DOI Open Access

Sandy Gerschler,

Sebastian Guenther, Christian Schulze

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13720 - 13720

Published: Nov. 8, 2022

Species of the genus Drosera, known for carnivorous plants, such as sundew, have been traditionally used centuries medicinal plants. Efficacy-determining compounds are naphthoquinones and flavonoids. Flavonoids possess a broad spectrum bioactive properties, including biofilm inhibitory activity. Biofilms render antibiotics ineffective, contributing to current rise in antimicrobial resistance. In this study, activity two European sundew species (Drosera rotundifolia Drosera intermedia) grown agriculturally Germany four commercial products (declared longifolia, sp. planta trit.) against three multidrug-resistant Escherichia coli strains was tested. The aim study comparatively investigate potential extracts locally northern products. minimum concentration approx. 35 µg mL-1. comparison, ranged from 75 140 Additionally, individual isolated were Among these compounds, determined eight substances, with 2″-O-galloyl hyperoside standing out its (38 mL-1). whole plant intermedia proved be more effective than single inhibition strains. Sundew may serve therapeutic approach targeting production.

Language: Английский

Citations

10
The circular bacteriocin enterocin NKR-5-3B has an improved stability profile over nisin DOI Creative Commons
Conan K. Wang, Yen‐Hua Huang,

Fatima Shabbir

et al.

Peptides, Journal Year: 2023, Volume and Issue: 167, P. 171049 - 171049

Published: June 28, 2023

Bacteriocins are a large family of bacterial peptides that have antimicrobial activity and potential applications as clinical antibiotics or food preservatives. Circular bacteriocins unique class these biomolecules distinguished by seamless circular topology, widely assumed to be ultra-stable based on this constraining structural feature. However, without quantitative studies their susceptibility defined thermal, chemical, enzymatic conditions, stability characteristics remain poorly understood, limiting translational development. Here, we produced the bacteriocin enterocin NKR-5-3B (Ent53B) in mg/L quantities using heterologous Lactococcus expression system, characterized its thermal NMR, chemical dichroism analytical HPLC, HPLC. We demonstrate Ent53B is ultra-stable, resistant temperatures approaching boiling, acidic (pH 2.6) alkaline 9.0) chaotropic agent 6 M urea, following incubation with range proteases (i.e., trypsin, chymotrypsin, pepsin, papain), conditions under which most proteins degrade. stable across broader pH than nisin, used manufacturing. Antimicrobial assays showed differences correlated bactericidal activity. Overall, study provides support for being an peptide molecules, suggesting easier handling distribution options available them practical agents.

Language: Английский

Citations

6
New cytotoxic dammarane type saponins from Ziziphus spina-christi DOI Creative Commons
Abeer H. Elmaidomy, Amr El Zawily, Aliasger K. Salem

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 23, 2023

Abstract Cancer is the world's second-leading cause of death. Drug development efforts frequently focus on medicinal plants since they are a valuable source anticancer medications. A phytochemical investigation edible Ziziphus spina-christi (F. Rhamnaceae) leaf extract afforded two new dammarane type saponins identified as christinin E and F ( 1, 2 ), along with known compound 3 ). Different cancer cell lines, such lung (A549), glioblastoma (U87), breast (MDA-MB-231), colorectal carcinoma (CT-26) were used to investigate extracted compounds' cytotoxic properties. Our findings showed significant effects all tested lines at varying concentrations (1, 5, 10, 20 µg/mL). The three compounds exhibited potent activity low (< 10 μg/mL), evidenced by their IC 50 values. To further complex relationships between these cancer-relevant biological targets identify critical in pathogenesis disease, we turned network pharmacology silico-based investigations. Following this, analysis (e.g., inverse docking, ΔG calculation, molecular dynamics simulation) was performed structures isolated additional potential for likely interactions various signalling pathways relevant this disease. Based our findings, Z. spina-christi's promise anti-cancer therapeutic leads future.

Language: Английский

Citations

5
Essential Oils from Southern Italian Aromatic Plants Synergize with Antibiotics against Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis Cell Growth and Biofilm Formation DOI Creative Commons

Giada Sena,

Elisabetta De Rose,

Michele Crudo

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(7), P. 605 - 605

Published: June 28, 2024

The spread of antibiotic-resistant pathogens has prompted the development novel approaches to identify molecules that synergize with antibiotics enhance their efficacy. This study aimed investigate effects ten Essential Oils (EOs) on activity nine in influencing growth and biofilm formation Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis. EOs alone combination both bacterial were analyzed by measuring MIC values through broth microdilution method crystal violet assay, respectively. All inhibited E. coli (1.25 ≤ 5 mg/mL) while P. aeruginosa faecalis was only affected from Origanum vulgare, (MIC = O. vulgare 1.25 Salvia rosmarinus mg/mL), In most induced a four- sixteen-fold reduction ampicillin, ciprofloxacin, ceftriaxone, gentamicin, streptomycin, such is observed combinations ciprofloxacin C. nepeta, bergamia, limon, reticulata, F. gentamicin tetracycline limon vulgare. A smaller effect which bergamia reduced concentration four-fold. EO-antibiotic also inhibit formation. More precisely, all showed highest percentage inhibition. Combinations induce up- down-methylation cytosines adenines compared EO or alone. provides evidence about role enhancing action key processes involved resistance mechanisms as epigenetic changes. Synergistic interactions should be effectively considered dealing pathogenic microorganisms.

Language: Английский

Citations

1
Lessons learnt from broad-spectrum coronavirus antiviral drug discovery DOI

Andrew A. Bolinger,

Jun Li, Xuping Xie

et al.

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: 19(9), P. 1023 - 1041

Published: July 30, 2024

Introduction Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East (MERS-CoV), and the most recent SARS-CoV-2 responsible for COVID-19 pandemic, pose significant threats to human populations over past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic distress syndromes (ARDS), resulting in high morbidity mortality.

Language: Английский

Citations

1