Use of Stem Cell-Derived Cardiomyocyte and Nasal Epithelium Models to Establish a Multi-Tissue Model Platform to Validate Repurposed Drugs Against SARS-CoV-2 Infection DOI Creative Commons
Nathan Gödde, Carmel O’Brien, Elizabeth Vincan

et al.

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

Published: May 23, 2024

Abstract The novel coronavirus disease (COVID-19) and any future outbreaks will require more affordable, effective safe treatment options to complement current ones such as Paxlovid . Drug repurposing can be a promising approach if we are able find rapid, robust reliable way down-select screen candidates using in silico vitro approaches. With repurposed drugs, ex vivo models could offer rigorous route human clinical trials with less time invested into nonclinical animal ( ) studies. We have previously shown the value of commercially available vivo/3D airway alveolar tissue models, this paper takes further by developing validating nasal epithelial model embryonic stem cells derived cardiomyocyte model. Five shortlisted (fluvoxamine, everolimus, pyrimethamine, aprepitant sirolimus) were successfully compared three control drugs (remdesivir, molnupiravir, nirmatrelvir) when tested against key variants SARS-CoV-2 virus including Delta Omicron, reconfirm our earlier finding that fluvoxamine induce antiviral efficacy combination other drugs. Scalability high-throughput screening has been demonstrated liquid handling robotic platform for ‘Disease-X’ outbreaks.

Language: Английский

Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2 DOI Creative Commons
Eduardo Martín-López,

Bowen Brennan,

Tianyang Mao

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(6), P. ENEURO.0106 - 24.2024

Published: June 1, 2024

Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use epithelial cells an entry point for infection. Within the nasal cavity, olfactory epithelium (OE) is particularly sensitive to infections which may lead dysfunction. In patients suffering from disease 2019, deficits in olfaction have been characterized a distinctive symptom. Here, we used K18hACE2 mice study spread of SARS-CoV-2 infection and inflammation system (OS) after 7 d OE, found that selectively targeted supporting/sustentacular (SCs) macrophages lamina propria. brain, infected some microglial bulb (OB), there was widespread projection neurons OB, piriform cortex (PC), tubular striatum (TuS). Inflammation, indicated by both elevated numbers morphologically activated IBA1 + (monocyte/macrophage lineages), preferentially increased OE septum, while it homogeneously distributed throughout layers PC, TuS. Myelinated OS axonal tracts, lateral tract, anterior commissure, exhibited decreased levels 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, indicative myelin defects. Collectively, our work supports hypothesis SC and, centrally, microglia subpopulations neurons. The observed areas central defects account long-lasting deficit.

Language: Английский

Citations

3
The Neurological Implications of COVID-19: A Comprehensive Narrative Review DOI Open Access
Ithamar Cheyne,

Venmanassery Sreejan Gopinath,

Neeharika Muppa

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: May 15, 2024

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 revealed a huge number of problems as well discoveries in medicine, notably, regarding effects virus on central nervous system (CNS) and peripheral (PNS). This paper is narrative review that takes deep dive into complex interactions between NS. Therefore, this explains broad range neurological manifestations neurodegenerative diseases virus. It carefully considers routes through which reaches NS, including olfactory course, hematogenous route, are also covered when discussing virus's direct indirect mechanisms neuropathogenesis. Besides pathologies such stroke, encephalitis, Guillain-Barré syndrome, Parkinson's disease, multiple sclerosis, focus area given to challenges making diagnosis, treatment, management these conditions during pandemic. examines strategic interventional approaches utilized prevent disorders, ACE2 receptors implicated mediation COVID-19. detailed overview, combines research outputs with case data, directed at tackling challenge, view toward better patient care outcomes future.

Language: Английский

Citations

2
Acute and long-term SARS-CoV-2 infection and neurodegeneration processes—circulus vitiosus DOI Creative Commons
Weronika D. Krahel, Michalina Bartak, Joanna Cymerys

et al.

Acta Virologica, Journal Year: 2024, Volume and Issue: 68

Published: Oct. 15, 2024

The global pandemic of COVID-19 caused by SARS-CoV-2 has had a devastating impact. Although many survived the acute effects pandemic, significant number survivors, including those with only mild symptoms, are now experiencing prolonged and debilitating post-viral syndrome known as LC/PASC (long COVID/post-acute sequelae SARS-CoV-2). Typical symptoms include fatigue, breathlessness, chest pain, impaired cognition, difficulty sleeping, fever gastrointestinal symptoms. Anxiety depression can also last for weeks to months range from disabling. association between neuropsychiatric infection raises questions about possible routes entry central nervous system (CNS) long-term virus on CNS, their molecular basis, potential risk neuronal damage associated subsequent development neurodegenerative diseases.

Language: Английский

Citations

2
Use of Stem Cell-Derived Cardiomyocyte and Nasal Epithelium Models to Establish a Multi-Tissue Model Platform to Validate Repurposed Drugs Against SARS-CoV-2 Infection DOI Creative Commons
Nathan Gödde, Carmel O’Brien, Elizabeth Vincan

et al.

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

Published: May 23, 2024

Abstract The novel coronavirus disease (COVID-19) and any future outbreaks will require more affordable, effective safe treatment options to complement current ones such as Paxlovid . Drug repurposing can be a promising approach if we are able find rapid, robust reliable way down-select screen candidates using in silico vitro approaches. With repurposed drugs, ex vivo models could offer rigorous route human clinical trials with less time invested into nonclinical animal ( ) studies. We have previously shown the value of commercially available vivo/3D airway alveolar tissue models, this paper takes further by developing validating nasal epithelial model embryonic stem cells derived cardiomyocyte model. Five shortlisted (fluvoxamine, everolimus, pyrimethamine, aprepitant sirolimus) were successfully compared three control drugs (remdesivir, molnupiravir, nirmatrelvir) when tested against key variants SARS-CoV-2 virus including Delta Omicron, reconfirm our earlier finding that fluvoxamine induce antiviral efficacy combination other drugs. Scalability high-throughput screening has been demonstrated liquid handling robotic platform for ‘Disease-X’ outbreaks.

Language: Английский

Citations

0