iPSC‐derived human cortical organoids display profound alterations of cellular homeostasis following SARS‐CoV‐2 infection and Spike protein exposure

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)

Published: Feb. 14, 2025

Abstract COVID‐19 commonly leads to respiratory issues, yet numerous patients also exhibit a diverse range of neurological conditions, suggesting detrimental impact SARS‐CoV‐2 or the viral Spike protein on central nervous system. Nonetheless, molecular pathway behind pathology and presumed neurotropism remains largely unexplored. We generated human cortical organoids (HCOs) derived from induced pluripotent stem cells (hiPSC) assess: (1) expression main entry factors; (2) their vulnerability infection; (3) infection exposure transcriptome. Results proved that HCOs express receptors co‐receptors; may be productively infected by SARS‐CoV‐2; particles released SARS‐CoV‐2‐infected are able re‐infect another cellular line; (4) resulted in activation apoptotic stress pathways, along with inflammatory processes. Notably, these effects were recapitulated when exposed alone. The data obtained demonstrate likely infects probably through binding ACE2, CD147, NRP1 factors. Furthermore, alone sufficient disrupt homeostasis induce neurotoxic effects, potentially contributing onset long‐COVID symptoms.

Language: Английский

---

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 167 - 178

Published: May 6, 2024

Language: Английский

---

Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2

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

---

Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8779 - 8779

Published: Aug. 12, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and suppressing both stress granules processing bodies, which postulated increase uncoated gRNA availability. N can also form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological, neuronal, glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms pathological over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependent on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modeling suggests condensate composed an quadriplex C terminus incorporated.

Language: Английский

---

Post COVID-19 Reflections and Questions: How Prepared Are We for the Next Pandemic?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 859 - 859

Published: Jan. 10, 2024

While the end of COVID-19 pandemic was announced earlier in 2023 by WHO, currently dominating virus variants, such as omicron sub-lineages XBB [...]

Language: Английский

---

Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains

Published: July 4, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and in also suppressing both stress granules processing bodies which postulated increase uncoated gRNA availability. N can form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological neuronal glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependant on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modelling suggests condensate formed composed quadriplex C terminus incorporated.

Language: Английский

---

SARS-CoV-2 natural infection, but not vaccine-induced immunity, elicits cross-reactive immunity to OC43

Heliyon, Journal Year: 2024, Volume and Issue: 10(19), P. e37928 - e37928

Published: Sept. 23, 2024

Language: Английский

---