Detection of Viral RNA Fragments in Human iPSC-Cardiomyocytes following Treatment with Extracellular Vesicles from SARS-CoV-2 Coding-Sequence-Overexpressing Lung Epithelial Cells

Kwon, Youjeong; Nukala, Sarath Babu; Srivastava, Shubhi; Miyamoto, Hiroe; Ismail, Nur Izzah; Ong, Sang‐Bing; Lee, Won Hee; Ong, Sang-Ging

doi:10.1101/2020.05.14.093583

Cited by 23 publications

(24 citation statements)

References 12 publications

(7 reference statements)

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“…The in vitro cell culture and tissue models will also be helpful in studying SARS-CoV-2 infection, cytotoxicity, molecular mechanisms, and drug or therapy effects on cells. As multiple studies have shown, the iPSC-derived cardiomyocytes could be transfected by SARS-CoV-2 and develop cytotoxic effects and death [ 61 , 136 , 137 , 138 , 139 , 140 ]. The use of cardiac organoids will be instructive to mimic COVID-19 infection of the heart but, as of now, there is no study available.…”

Section: Limitations Of Animal Modelsmentioning

confidence: 99%

Cardiovascular Manifestations of COVID-19 Infection

Magadum

Kishore

2020

Cells

189

136

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SARS-CoV-2 induced the novel coronavirus disease (COVID-19) outbreak, the most significant medical challenge in the last century. COVID-19 is associated with notable increases in morbidity and death worldwide. Preexisting conditions, like cardiovascular disease (CVD), diabetes, hypertension, and obesity, are correlated with higher severity and a significant increase in the fatality rate of COVID-19. COVID-19 induces multiple cardiovascular complexities, such as cardiac arrest, myocarditis, acute myocardial injury, stress-induced cardiomyopathy, cardiogenic shock, arrhythmias and, subsequently, heart failure (HF). The precise mechanisms of how SARS-CoV-2 may cause myocardial complications are not clearly understood. The proposed mechanisms of myocardial injury based on current knowledge are the direct viral entry of the virus and damage to the myocardium, systemic inflammation, hypoxia, cytokine storm, interferon-mediated immune response, and plaque destabilization. The virus enters the cell through the angiotensin-converting enzyme-2 (ACE2) receptor and plays a central function in the virus’s pathogenesis. A systematic understanding of cardiovascular effects of SARS-CoV2 is needed to develop novel therapeutic tools to target the virus-induced cardiac damage as a potential strategy to minimize permanent damage to the cardiovascular system and reduce the morbidity. In this review, we discuss our current understanding of COVID-19 mediated damage to the cardiovascular system.

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Section: Limitations Of Animal Modelsmentioning

confidence: 99%

Cardiovascular Manifestations of COVID-19 Infection

Magadum

Kishore

2020

Cells

189

136

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“…Moreover, exosomes secreted by the adult CPe can be hijacked to serve as a vehicle for the spread of virus infection from periphery to the CNS as shown for human polyomavirus (JCPyV) [131]. Intriguingly, CP-mediated release of exosomes may underlie transmission of SARS-coronavirus 2 (SARS-CoV-2) within the CNS as the CP displays relatively-high expression levels of ACE2 receptor, which is engaged by SARS-CoV-2 for active invasion of host cells [132][133][134][135].…”

Section: Exosomes In Cp-csf Signallingmentioning

confidence: 99%

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Kaiser

Bryja

2020

IJMS

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Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.

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“…Interestingly, cardiac injury has been reported in COVID-19 patients [ 100 ], even in the absence of coronary arteries obstruction [ 101 ], therefore unlikely to be caused by altered coagulation observed in these patients [ 102 ]. Furthermore, a mechanism of entry of SARS-CoV-2 in cardiomyocytes has been recently proposed [ 103 ]. In light of these evidences, should the cardiac injury, observed in COVID-19 patients, be proven to be due, at least in part, to cavinin-1 sequestration by viral N, then inhibitors of the N-cavinin1 interaction may be valuable drug candidates.…”

Section: Discussionmentioning

confidence: 99%

Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics

Terracciano

Preianò

Fregola

et al. 2021

IJMS

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Protein–protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage to obtain a “high resolution” view of virus–host interactions has come true. In fact, the rapidly expanding approaches of mass spectrometry (MS)-based proteomics in the study of PPIs provide efficient tools to identify a significant number of potential drug targets. Generation of PPIs maps by affinity purification-MS and by the more recent proximity labeling-MS may help to uncover cellular processes hijacked and/or altered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing promising therapeutic targets. The possibility to further validate putative key targets from high-confidence interactions between viral bait and host protein through follow-up MS-based multi-omics experiments offers an unprecedented opportunity in the drug discovery pipeline. In particular, drug repurposing, making use of already existing approved drugs directly targeting these identified and validated host interactors, might shorten the time and reduce the costs in comparison to the traditional drug discovery process. This route might be promising for finding effective antiviral therapeutic options providing a turning point in the fight against the coronavirus disease-2019 (COVID-19) outbreak.

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Detection of Viral RNA Fragments in Human iPSC-Cardiomyocytes following Treatment with Extracellular Vesicles from SARS-CoV-2 Coding-Sequence-Overexpressing Lung Epithelial Cells

Cited by 23 publications

References 12 publications

Cardiovascular Manifestations of COVID-19 Infection

Cardiovascular Manifestations of COVID-19 Infection

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics

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