Dynamic metabolic modeling of ATP allocation during viral infection DOI Creative Commons
A. Hacibektascedilla ̃oghacek ̃lu, Ilija Dukovski, Daniel Segrè

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 13, 2024

Viral pathogens, like SARS-CoV-2, hijack the host's macromolecular production machinery, imposing an energetic burden that is distributed across cellular metabolism. To explore dynamic metabolic tension between survival and viral replication, we developed a computational framework uses genome-scale models to perform Flux Balance Analysis of human cell metabolism during virus infections. Relative previous models, our addresses physiology infections non-proliferating host cells through two new features. First, by incorporating lipid content SARS-CoV-2 biomass, discovered activation previously overlooked pathways giving rise predictions possible drug targets. Furthermore, introduce model simulates partitioning resources cell, capturing extent which competition depletes from essential ATP. By dynamics into COMETS for spatio-temporal modeling metabolism, provide mechanistic, generalizable starting point bridging systems biology with pathogenesis. This could be extended broadly incorporate phage in microbial ecosystems.

Язык: Английский

Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reíter

Exploration of neuroscience, Год журнала: 2025, Номер 4

Опубликована: Март 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Язык: Английский

Процитировано

0

Metabolic modelling reveals key pathways in COVID-19 in an effort to drive drug purposing DOI Open Access
Alexandre Oliveira, Miguel Rocha, Óscar Dias

и другие.

IFAC-PapersOnLine, Год журнала: 2024, Номер 58(23), С. 91 - 96

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0

Dynamic metabolic modeling of ATP allocation during viral infection DOI Creative Commons
A. Hacibektascedilla ̃oghacek ̃lu, Ilija Dukovski, Daniel Segrè

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 13, 2024

Viral pathogens, like SARS-CoV-2, hijack the host's macromolecular production machinery, imposing an energetic burden that is distributed across cellular metabolism. To explore dynamic metabolic tension between survival and viral replication, we developed a computational framework uses genome-scale models to perform Flux Balance Analysis of human cell metabolism during virus infections. Relative previous models, our addresses physiology infections non-proliferating host cells through two new features. First, by incorporating lipid content SARS-CoV-2 biomass, discovered activation previously overlooked pathways giving rise predictions possible drug targets. Furthermore, introduce model simulates partitioning resources cell, capturing extent which competition depletes from essential ATP. By dynamics into COMETS for spatio-temporal modeling metabolism, provide mechanistic, generalizable starting point bridging systems biology with pathogenesis. This could be extended broadly incorporate phage in microbial ecosystems.

Язык: Английский

Процитировано

0