Inflammasome activation at the crux of severe COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(11), P. 694 - 703

Published: Aug. 9, 2021

Language: Английский

---

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

---

Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice

EBioMedicine, Journal Year: 2021, Volume and Issue: 75, P. 103803 - 103803

Published: Dec. 31, 2021

The Coronavirus Disease 2019 (COVID-19) pandemic has been a great threat to global public health since 2020. Although the advance on vaccine development largely achieved, strategy alleviate immune overactivation in severe COVID-19 patients is still needed. NLRP3 inflammasome activated upon SARS-CoV-2 infection and associated with severity. However, processes by which involved disease remain unclear.We infected THP-1 derived macrophages, knockout mice, human ACE2 transgenic mice live Biosafety Level 3 (BSL-3) laboratory. We performed quantitative real-time PCR for targeted viral or host genes from mouse tissues, conducted histological immunofluorescence analysis tissues. also injected intranasally AAV-hACE2 intraperitoneally inhibitor MCC950 before as indicated.We have provided multiple lines of evidence that plays an important role response invasion lungs. Inhibition attenuated release related pro-inflammatory cytokines cell cultures mice. pathology induced lung tissues was reduced Nlrp3-/- compared wild-type C57BL/6 Finally, specific inhibition alleviated excessive inflammation thus like mice.Inflammatory activation stimulator immunopathology. Targeting promising intervention against disease.This work supported grants Bureau Frontier Sciences Education, CAS (grant no. QYZDJ-SSW-SMC005 Y.G.Y.), key project "Light West China" Program (to D.Y.) Yunnan Province (202001AS070023 D.Y.).

Language: Английский

---

Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 6, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how evades antibodies. Here, we report novel mechanism extracellular vesicle (EV)-mediated cell-to-cell transmission SARS-CoV-2, which facilitates escape from These EVs, initially observed in envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected including Vero E6, Calu-3, HPAEpiC undergoing infection-induced pyroptosis. Various cells produce similar EVs characterized extra-large sizes (1.6-9.5 μm diameter, average diameter > 4.2 μm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis plaque assay reveal that these SARS-CoV-2-induced contain large amounts live virus particles. particular, vesicle-cloaked antibodies able reinfect naïve independent receptors cofactors. Consistently, constructed 3D images show intact could be taken up recipient directly, supporting vesicle-mediated SARS-CoV-2. Our findings receptor-independent infection via transmission, provide new insights into suggest potential targets for future antiviral therapeutics.

Language: Английский

---

SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114242 - 114242

Published: Jan. 11, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, which seriously affected human health worldwide. The discovery of therapeutic agents is extremely urgent, and the viral structural proteins are particularly important as potential drug targets. SARS-CoV-2 envelope (E) protein one main virus, involved in multiple processes virus life cycle directly related to pathogenesis process. In this review, we present amino acid sequence E compare it with other two coronaviruses. We then explored role discussed pathogenic mechanisms that may be in. Next, summarize drugs against discovered current studies. Finally, described possible effects mutation on host. This established knowledge system date, aiming provide theoretical insights for mitigating COVID-19 pandemic future outbreaks.

Language: Английский

---

The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 3, 2023

Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has a global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it potential target therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with catalyzes ubiquitination E on 63rd lysine, leading to degradation ubiquitin-proteasome system (UPS). Importantly, RNF5-induced inhibits SARS-CoV-2 replication pharmacological activator Analog-1 alleviates development in mouse infection model. We also found distinctively expressed different age groups patients displaying severity, may be exploited as prognostic marker Furthermore, recognized from various strains SARS-CoV, suggesting targeting broad-spectrum antiviral strategy. Our findings provide novel insights into role UPS antagonizing replication, opens new avenues therapeutic intervention combat COVID-19 pandemic.

Language: Английский

---

Characterization of the SARS‐CoV‐2 E Protein: Sequence, Structure, Viroporin, and Inhibitors

Protein Science, Journal Year: 2021, Volume and Issue: 30(6), P. 1114 - 1130

Published: April 4, 2021

The COVID-19 epidemic is one of the most influential epidemics in history. Understanding impact coronaviruses (CoVs) on host cells very important for disease treatment. SARS-CoV-2 envelope (E) protein a small structural involved many aspects viral life cycle. E promotes packaging and reproduction virus, deletion this weakens or even abolishes virulence. This review aims to establish new knowledge by combining recent advances study comparing it with SARS-CoV protein. amino acid sequence, structure, self-assembly characteristics, viroporin mechanisms inhibitors are summarized analyzed herein. Although proteins similar respects, specific studies protein, both monomers oligomers, still lacking. A comprehensive understanding should prompt further design characterization effective targeted therapeutic measures.

Language: Английский

---

The envelope protein of SARS‐CoV‐2 increases intra‐Golgi pH and forms a cation channel that is regulated by pH

The Journal of Physiology, Journal Year: 2021, Volume and Issue: 599(11), P. 2851 - 2868

Published: March 12, 2021

We report a novel method for the transient expression of SARS-CoV-2 envelope (E) protein in intracellular organelles and plasma membrane mammalian cells Xenopus oocytes. Intracellular E increases intra-Golgi pH. By targeting to membrane, we show that it forms cation channel, viroporin, is modulated by changes This studying activity viroporins may facilitate screening new antiviral drugs identify treatments COVID-19.The coronaviruses such as SARS-CoV-1 proposed form an ion channel or viroporin participates viral propagation pathogenesis. Here developed technique study directed using carboxyl-terminal fluorescent tag, mKate2. The wild-type can be trafficked organelles, notably endoplasmic reticulum-Golgi intermediate complex, where its pH inside organelle. also succeeded which enabled biophysical analysis whole-cell patch clamp recording cell line, HEK 293 cells, two-electrode voltage electrophysiology results suggest permeable monovalent cations Na+ , Cs+ K+ . current nearly time- voltage-independent when expressed At 6.0 7.4, activated, whereas at 8.0 9.0, amplitude reduced, oocytes inward fades 9 voltage-dependent manner. Using this electrophysiological recordings, potential inhibitors screened subsequently investigated against vitro possible efficacy treating COVID-19.

Language: Английский

---

Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 13, 2022

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has dramatically influenced various aspects the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies prevent treat this threatening disease. universally acknowledged that cell death autophagy are essential crucial maintaining host homeostasis participating in pathogenesis. At present, more than twenty different types have been discovered, some parts which fully understood, whereas need investigation. Increasing studies indicated might play an important role virus pathogenicity. However, knowledge interactions related SARS-CoV-2 between lacks systematic elucidation. Therefore, review, we comprehensively delineate how manipulates diverse (including apoptosis, necroptosis, pyroptosis, ferroptosis, NETosis) itself benefits, simultaneously involved occurrence progression COVID-19, aiming provide a reasonable basis existing interventions further development novel therapies.

Language: Английский

---

Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2

The International Journal of Biochemistry & Cell Biology, Journal Year: 2022, Volume and Issue: 145, P. 106185 - 106185

Published: Feb. 24, 2022

Language: Английский

---