scholarly journals Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yining Wang ◽  
Pengfei Li ◽  
Sajjan Rajpoot ◽  
Uzma Saqib ◽  
Peifa Yu ◽  
...  
Keyword(s):  
Cell Culture ◽  
Molecular Docking ◽  
Synergistic Effects ◽  
3D Structure ◽  
Specific Treatment ◽  
Binding Affinities ◽  
Human Coronavirus ◽  
Culture Models ◽  
Cell Culture Models

AbstractHuman coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively. The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp. In cell culture models infected with HCoV-NL63, both favipiravir and remdesivir significantly inhibited viral replication and production of infectious viruses. Overall, remdesivir compared to favipiravir is more potent in inhibiting HCoV-NL63 in cell culture. Importantly, there is no evidence of resistance development upon long-term exposure to remdesivir. Furthermore, combining favipiravir or remdesivir with the clinically used antiviral cytokine interferon-alpha resulted in synergistic effects. These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection.

scholarly journals A Pilot Study To Establish an In Vitro Model To Study Premature Intestinal Epithelium and Gut Microbiota Interactions

mSphere ◽  
2021 ◽  
Author(s):  
Justin Gibbons ◽  
Ji Youn Yoo ◽  
Tina Mutka ◽  
Maureen Groer ◽  
Thao T. B. Ho
Keyword(s):  
Cell Culture ◽  
In Vitro Model ◽  
Bacterial Flora ◽  
Mucosal Barrier ◽  
Clinical Observations ◽  
Culture Models ◽  
Vitro Model ◽  
Cell Culture Models

The gut bacterial flora influences the development of the immune system and long-term health outcomes in preterm infants. Studies of the mechanistic interactions between the gut bacteria and mucosal barrier are limited to clinical observations, animal models, and in vitro cell culture models for this vulnerable population.

Abstract A127: Long-term cell culture models enable drug response determination for epigenetic therapeutics.

2013 ◽  
Author(s):  
Jim Hnilo ◽  
Katie Snead ◽  
Karen Bernards ◽  
Brian Nelson ◽  
Keith McKinley ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Response ◽  
Culture Models ◽  
Response Determination ◽  
Cell Culture Models

Abstract 4259: Long term cell culture models to identify biomarkers of response

2016 ◽  
Author(s):  
Usha Warrior ◽  
Jonathan Crane ◽  
Karen Bernards ◽  
Brian Nelson ◽  
Katie Snead ◽  
...  
Keyword(s):  
Cell Culture ◽  
Culture Models ◽  
Cell Culture Models

scholarly journals Inhibition of synucleinopathic seeding by rationally designed inhibitors

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Smriti Sangwan ◽  
Shruti Sahay ◽  
Kevin A Murray ◽  
Sophie Morgan ◽  
Elizabeth L Guenther ◽  
...  
Keyword(s):  
Cell Culture ◽  
Molecular Basis ◽  
Binding Affinities ◽  
Human Patient ◽  
The Core ◽  
Lack Of Information ◽  
Culture Models ◽  
Cell Culture Models ◽  
Rapid Conversion

Seeding, in the context of amyloid disease, is the sequential transfer of pathogenic protein aggregates from cell-to-cell within affected tissues. The structure of pathogenic seeds provides the molecular basis and enables rapid conversion of soluble protein into fibrils. To date, there are no inhibitors that specifically target seeding of Parkinson’s disease (PD)-associated α-synuclein (α-syn) fibrils, in part, due to lack of information of the structural properties of pathological seeds. Here we design small peptidic inhibitors based on the atomic structure of the core of α-syn fibrils. The inhibitors prevent α-syn aggregation in vitro and in cell culture models with binding affinities of 0.5 μM to α-syn fibril seeds. The inhibitors also show efficacy in preventing seeding by human patient-derived α-syn fibrils. Our results suggest that pathogenic seeds of α-syn contain steric zippers and suggest a therapeutic approach targeted at the spread and progression that may be applicable for PD and related synucleinopathies.

Long-term cell culture models for the analysis of hepatotoxicity in vitro

2007 ◽  
Vol 172 ◽  
pp. S97-S98
Author(s):  
Gregor Tuschl ◽  
Jens Hrach ◽  
Lysiane Richert ◽  
Lysiane Richert ◽  
Christophe Chesné ◽  
...  
Keyword(s):  
Cell Culture ◽  
Culture Models ◽  
Cell Culture Models

scholarly journals Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

2021 ◽  
Author(s):  
Terry Riss ◽  
O. Joseph Trask
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
Fluorescent Imaging ◽  
Culture Models ◽  
Assay Methods ◽  
Diffusion Rates ◽  
Cell Culture Models ◽  
Dimensional Cell ◽  
Cells Cultured

AbstractAlong with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.

scholarly journals Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis

2006 ◽  
Vol 26 (17) ◽  
pp. 6425-6434 ◽  
Author(s):  
O. Jameel Shah ◽  
Tony Hunter
Keyword(s):  
Cell Culture ◽  
Tuberous Sclerosis ◽  
High Speed ◽  
Serine Phosphorylation ◽  
Feedback Signal ◽  
Insulin Receptor Substrates ◽  
Igf I ◽  
Culture Models ◽  
Cell Culture Models

ABSTRACT The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

Cell culture models of the ocular barriers

2005 ◽  
Vol 60 (2) ◽  
pp. 207-225 ◽  
Author(s):  
Margit Hornof ◽  
Elisa Toropainen ◽  
Arto Urtti
Keyword(s):  
Cell Culture ◽  
Culture Models ◽  
Cell Culture Models
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