Disruptive 3D in vitro models for respiratory disease investigation: A state-of-the-art approach focused on SARS-CoV-2 infection DOI Creative Commons

Maria Luiza Seixas,

Cynthia Silva Bartolomeo, Robertha Mariana Rodrigues Lemes

et al.

Biomaterials and Biosystems, Journal Year: 2023, Volume and Issue: 11, P. 100082 - 100082

Published: July 16, 2023

COVID-19, along with most respiratory diseases in the medical field, demonstrates significant ability to take its toll on global population. There is a particular difficulty studying these conditions, which stems especially from short supply of vitro models for detailed investigation, specific therapeutic knowledge required disease scrutinization and occasional need BSL-3 [Biosafety Level 3] laboratories research. Based this, process drug development hampered great extent. In scenario this even more substantial account current undefinition regarding exact role ACE2 [Angiotensin-converting enzyme 2] receptor upon SARS-CoV-2 kinetics human cells level demand investigation ACE2, usually requires laborious ethically complicated usage transgenic animal overexpressing receptor. Moreover, rapid progression aforementioned diseases, poses crucial necessity adequate solutions emergence. context, work herein presented introduces groundbreaking set 3D models, namely spheroids MatriWell cell culture inserts, whose remarkable mimic vivo environment makes them highly suitable particularly infection. Using MatriWells, we developed an innovative platform COVID-19 research: pulmonary air-liquid interface [ALI] associated endothelial (HUVEC) cells. Infection studies revealed that (BEAS-2B) ALI reached peak viral load at 24h cells, 48h, demonstrating lung replication subsequent hematogenous dissemination, provides us unique realistic framework COVID-19. Simultaneously, were used address understudied receptor, aiming pronounced investigation. expression not only increased spheroid diameter by 20% (p<0.001) volume 60% (p≤0.0001) but also led 640-fold increase intracellular (p≤0.01). The previously mentioned finding supports as potential target treatment. Lastly, observed higher MatriWells compared (150-fold, p<0.0001), suggesting appropriate approach By establishing advanced method tract conditions research, paves way toward efficacious development, contributing change course such

Language: Английский

SARS-CoV-2 variants evolve convergent strategies to remodel the host response DOI Creative Commons
Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4597 - 4614.e26

Published: Sept. 21, 2023

Language: Английский

Citations

68
Modelling host–microbiome interactions in organ-on-a-chip platforms DOI
Yong Cheol Shin, Nam Than, So‐Youn Min

et al.

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 2(2), P. 175 - 191

Published: Nov. 17, 2023

Language: Английский

Citations

19
Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics DOI Creative Commons
Dario Valter Conca, Fouzia Bano,

Julius von Wirén

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 10, 2024

Abstract The worldwide spread of SARS-CoV-2 has been characterised by the emergence several variants concern (VOCs) presenting an increasing number mutations in viral genome. spike glycoprotein, responsible for engaging receptor ACE2, exhibits highest density mutations, suggesting ongoing evolution to optimize entry. However, previous studies focussed on isolated molecular interactions, neglecting intricate composition plasma membrane and interplay between attachment factors. Our study explores role avidity complexity modulating virus-host binding kinetics during early stages entry original Wuhan strain three VOCs: Omicron BA.1, Delta, Alpha. We employ fluorescent liposomes decorated with from VOCs as virion mimics single-particle tracking native supported lipid bilayers derived pulmonary Calu-3 cells. findings reveal increase affinity multivalent bond cell surface driven increased association rate. show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed cells’ membrane, plays central interaction we observe shift its screening ACE2 important factor Omicron. This is caused ∼10-fold Omicron’s HS compared strain, shown using atomic force microscopy-based single-molecule spectroscopy. results importance coreceptors, particularly HS, modulation VOCs. highlight transition variants’ strategy towards use initial docking site, which likely shaping tropism infection upper airways, milder symptoms, higher transmissibility.

Language: Английский

Citations

5
SARS-CoV-2 Infection Alters the Phenotype and Gene Expression of Adipocytes DOI Open Access
Paola Quaranta, Gaia Scabia, Barbara Storti

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2086 - 2086

Published: Feb. 8, 2024

Epidemiological evidence emphasizes that excess fat mass is associated with an increased risk of severe COVID-19 disease. Nevertheless, the intricate interplay between SARS-CoV-2 and adipocytes remains poorly understood. It crucial to decipher progression both in acute phase on long-term outcomes. In this study, vitro model using human SGBS cell line (Simpson-Golabi-Behmel syndrome) was developed investigate infectivity adipocytes, effects virus exposure adipocyte function. Our results show expressing ACE2 are susceptible infection, as evidenced by release viral genome into medium, detection nucleocapsid lysates, positive immunostaining for spike protein. Infected remarkable changes compared uninfected controls: surface area lipid droplets, upregulated expression genes inflammation (

Language: Английский

Citations

5
Recombinant Rod Domain of Vimentin Reduces SARS-CoV-2 Viral Replication by Blocking Spike Protein–ACE2 Interactions DOI Open Access
Fong Lam, Cameron A. Brown,

Shannon E. Ronca

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2477 - 2477

Published: Feb. 20, 2024

Although the SARS-CoV-2 vaccination is primary preventive intervention, there are still few antiviral therapies available, with current drugs decreasing viral replication once virus intracellular. Adding novel to target additional points in life cycle paramount preventing future pandemics. The purpose of this study was create and test a protein decrease replication. We created recombinant rod domain vimentin (rhRod) E. coli used biolayer interferometry measure its affinity S1S2 spike ability block SARS-CoV-2–ACE2 interaction. performed plaque assays rhRod’s effect on Vero E6 cells. Finally, we measured lung inflammation SARS-CoV-2-exposed K18-hACE transgenic mice given intranasal intraperitoneal rhRod. found that rhRod has high for strong S1S2–ACE2 interactions. daily addition decreased cells starting at 48 h concentrations >1 µM. SARS-CoV-2-infected receiving had compared mock-treated animals. Based our data, decreases vitro vivo. Future studies will need evaluate protective effects against variants identify optimal dosing scheme both prevents host injury.

Language: Английский

Citations

4
Models and cellular monolayers to study the effect of SARS-CoV-2 on kidney DOI
Pragya Singh,

Kumar Sharma

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 533 - 542

Published: Jan. 1, 2025

Language: Английский

Citations

0
A web-based artificial intelligence system for label-free virus classification and detection of cytopathic effects DOI Creative Commons
Zeynep Akkutay-Yoldar,

Mehmet Türkay Yoldar,

Yiğit Burak Akkaş

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 18, 2025

Identifying viral replication within cells demands labor-intensive isolation methods, requiring specialized personnel and additional confirmatory tests. To facilitate this process, we developed an AI-powered automated system called AI Recognition of Viral CPE (AIRVIC), specifically designed to detect classify label-free cytopathic effects (CPEs) induced by SARS-CoV-2, BAdV-1, BPIV3, BoAHV-1, two strains BoGHV-4 in Vero MDBK cell lines. AIRVIC utilizes convolutional neural networks, with ResNet50 as the primary architecture, trained on 40,369 microscopy images at various magnifications. demonstrated strong detection, achieving 100% accuracy for DN-599 strain cells, highest among tested strains. In contrast, MOVAR 33/63 showed a lower 87.99%, lowest all models tested. For virus classification, multi-class 87.61% was achieved bovine viruses cells; however, it dropped 63.44% when identified without specifying line. best our knowledge, is first research article published English utilize distinguishing animal infections culture. AIRVIC's hierarchical structure highlights its adaptability virological diagnostics, providing unbiased infectivity scoring facilitating antiviral efficacy testing. Additionally, accessible web-based platform, allowing global researchers leverage capabilities diagnostics beyond.

Language: Английский

Citations

0
CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex DOI Creative Commons
Ildar Gabaev,

Alexandra Rowland,

Emilija Jovanovic

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 7, 2025

Abstract The TMPRSS2 cell surface protease is used by a broad range of respiratory viruses to facilitate entry into target cells. Together with ACE2, represents key factor for SARS-CoV-2 infection, as mediates cleavage viral spike protein, enabling direct fusion the envelope host membrane. Since start COVID-19 pandemic, has gained attention therapeutic inhibitors which would inhibit but little known about regulation, particularly in types physiologically relevant infection. Here, we performed an unbiased genome-wide CRISPR-Cas9 library screen, together targeted at epigenetic modifiers and transcriptional regulators, identify cellular factors that modulate expression human colon epithelial We find endogenous regulated Elongin BC-VHL complex HIF transcription factors. Depletion B or treatment cells PHD resulted downregulation inhibition show still utilised Omicron variants colonic Our study enhances our understanding regulation

Language: Английский

Citations

0
Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity DOI Creative Commons
Quy Xiao Xuan Lin, Deepa Rajagopalan, Akshamal M. Gamage

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 18, 2024

Due to the paucity of longitudinal molecular studies COVID-19, particularly those covering early stages infection (Days 1-8 symptom onset), our understanding host response over disease course is limited. We perform single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with samples. examine discrete subtypes continuous states longitudinally, we identify upregulation type I IFN-stimulated genes (ISGs) as predominant signature subsequent worsening symptoms, which validate in an independent cohort corroborate by plasma markers. However, ISG expression dynamic progressors, spiking then rapidly receding level severity-matched non-progressors. In contrast, cross-sectional analysis shows that deficient IFN suppressors such SOCS3 are upregulated severe critical COVID-19. latter four cohorts, inhibition reduces SARS-CoV-2 replication vitro. summary, complexity well a potential avenue for host-directed therapy.

Language: Английский

Citations

3
Development of animal models for emerging infectious diseases by breaking the barrier of species susceptibility to human pathogens DOI Creative Commons

Na Rong,

Jiangning Liu

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 7, 2023

Outbreaks of emerging infectious diseases pose a serious threat to public health security, human and economic development. After an outbreak, animal model for disease is urgently needed studying the etiology, host immune mechanisms pathology disease, evaluating efficiency vaccines or drugs against infection, minimizing time available development, which usually hindered by nonsusceptibility common laboratory animals pathogens. Thus, we summarize technologies methods that induce susceptibility pathogens, include viral receptor humanization, pathogen-targeted tissue immunodeficiency induction screening naturally susceptible species. Furthermore, advantages deficiencies models developed using each method were analyzed, these will guide selection potentially reduce develop during epidemics.

Language: Английский

Citations

9