Discovery of novel SARS-CoV-2 3CLpro inhibitors from natural products by FRET-based assay DOI Creative Commons
Tianyu Zhang,

Xianlong Ye,

Jixia Wang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Abstract As a highly conserved protease, 3-chymotrypsin-like protease (3CLpro) plays key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, and drugs targeting 3CLpro have shown promising therapeutic effects. Promising applications been achieved with direct-acting antivirals 3CLpro. Natural products are an important source of medicinal compounds. In this study, we expressed purified fusion proteins obtained soluble 3CLpro, the enzymatic activity was evaluated using fluorescence resonance energy transfer (FRET) assays at optimized concentrations substrate. This assay further applied to validate inhibitory 30 compounds selected from 583 via virtual screening. Epitheaflagallin 3-O-gallate (ETFGg) identified binding free − 66.90 kcal/mol IC50 value 8.73 ± 2.30 µM for ligand-protein interaction study. Dynamics simulation results suggested that ETFGg interacted HIE163, THR190 GLN192 stable pocket during simulation. Together, work as inhibitor prominent capability, which could serve potential lead compound drug development against COVID-19.

Язык: Английский

Discovery of Novel SARS-CoV-2 3CLpro Inhibitors from Natural Products by FRET-Based Assay DOI
Tianyu Zhang, Jixia Wang,

Xianlong Ye

и другие.

Опубликована: Янв. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Язык: Английский

Процитировано

0
Shedding light on Paraconiothyrium brasiliense: Secondary metabolites, biological activities, and computational studies DOI Open Access
Sabrin R. M. Ibrahim, Abdulrahim A. Alzain,

Fatima A. Elbadwi

и другие.

Journal of Applied Pharmaceutical Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Fungi are renowned as a prolific source for the biosynthesis of therapeutically valuable metabolites. Paraconiothyrium genus (Leptosphaeriaceae) demonstrates remarkable potential wide array metabolites, including macrolides, terpenoids, polyketides, phenolics, and furanones, which exhibit diverse bioactivities. The present review focused on reported metabolites derived from brasiliense, their chemical structures bioactive properties. Furthermore, it delves into elucidation biosynthetic pathways these This encompasses description over 92 compounds in literature 2010 to October 2023. In addition, silico studies may explain mechanisms underlying neuroprotective properties certain furanone derivatives against central nervous system disorders. Among tested KEAP1 through Keap1/Nrf2 pathway-mediated neuroprotection, paraconfuranone I (48), (50), L (51) displayed docking scores ranging −6.158 −6.612 kcal/mol, similar exciting reference compound achieved highest score −6.633 kcal/mol. Moreover, new activities some inhibitors LasR target Pseudomonas aeruginosa were elucidated using molecular absorption, distribution, metabolism, excretion, toxicity prediction. Specifically, 1-(1’,2’-dideoxy-α-D-nucleopyranosyl)-β-carboline (73) had at −11.327 followed by 1-acetyl-β-carboline (75) −10.055 comparison (docking −10.023 kcal/ mol). ten other competitive −9.813 −9.312 mol. suggested P. brasiliense promising lead antibacterial agents.

Язык: Английский

Процитировано

0
Paraherquamides – A new hope and great expectations of anthelmintic agents: Computational studies DOI Creative Commons
Anfal S. Aljahdali, Abdelsattar M. Omar, Gamal A. Mohamed

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(11), С. e0312009 - e0312009

Опубликована: Ноя. 7, 2024

Nematode infections impose a significant health and economic burden, particularly as parasites develop resistance to existing treatments evade host defenses. This study explores the efficacy of 48 paraherquamide analogs, class polycyclic spiro-oxindole alkaloids with unique structural features, potential anthelmintic agents. Employing advanced computational methods, including molecular docking, MM-GBSA, dynamics simulations, we assessed interaction these analogs Ls-AchBP receptor, model for nematode neurotransmission. Among studied, Paraherquamide K, Mangrovamide A, Chrysogenamide A showed comparable docking MM-GBSA scores native antagonist. Notably, their binding interactions exhibited slight distinction attributed differences, such absence di-oxygenated 7-membered ring. Additionally, demonstrated robust stability in dynamic simulation studies favorable pharmacokinetic properties our in-silico ADME assessment. The insights gained from highlight basis developing new therapeutics infections. promising results this analysis set stage subsequent in-vivo validations pre-clinical studies, contributing arsenal against parasitic resistance.

Язык: Английский

Процитировано

0
Discovery of novel SARS-CoV-2 3CLpro inhibitors from natural products by FRET-based assay DOI Creative Commons
Tianyu Zhang,

Xianlong Ye,

Jixia Wang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Abstract As a highly conserved protease, 3-chymotrypsin-like protease (3CLpro) plays key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, and drugs targeting 3CLpro have shown promising therapeutic effects. Promising applications been achieved with direct-acting antivirals 3CLpro. Natural products are an important source of medicinal compounds. In this study, we expressed purified fusion proteins obtained soluble 3CLpro, the enzymatic activity was evaluated using fluorescence resonance energy transfer (FRET) assays at optimized concentrations substrate. This assay further applied to validate inhibitory 30 compounds selected from 583 via virtual screening. Epitheaflagallin 3-O-gallate (ETFGg) identified binding free − 66.90 kcal/mol IC50 value 8.73 ± 2.30 µM for ligand-protein interaction study. Dynamics simulation results suggested that ETFGg interacted HIE163, THR190 GLN192 stable pocket during simulation. Together, work as inhibitor prominent capability, which could serve potential lead compound drug development against COVID-19.

Язык: Английский

Процитировано

0