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

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NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases—An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 999 - 999

Published: March 23, 2023

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant players such as microglia/monocytes typically exhibit strong NLRP3 inflammasome activation. Hence idea suppression might solve neurodegenerative ailments. Here we review recent Literature about this topic. First, update conditions mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, ethnic/pharmacological agents/extracts regulating function. Second, pinpoint NLRP3-activating mechanisms known inhibition effects in (ischemia, stroke, hemorrhage), (Alzheimer’s disease, Parkinson’s Huntington’s MS, ALS), virus-induced (Zika, SARS-CoV-2, others) diseases. The available data show (i) disease-specific divergent activate (mainly animal) brains NLRP3; (ii) no evidence proves modifies (yet ad hoc trials ongoing); (iii) findings exclude concurrently activated other-than-NLRP3 inflammasomes functionally replace inhibited NLRP3. Finally, highlight among causes persistent therapies species difference problem disease models preference symptomatic over etiologic therapeutic approaches. Therefore, posit neural cell-based could drive etiological, pathogenetic, advances, NLRP3’s other inflammasomes’ regulation, while minimizing failure risks candidate drug trials.

Language: Английский

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Microbial membrane transport proteins and their biotechnological applications

World Journal of Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 40(2)

Published: Jan. 16, 2024

Abstract Because of the hydrophobic nature membrane lipid bilayer, majority hydrophilic solutes require special transportation mechanisms for passing through cell membrane. Integral transport proteins (MTPs), which belong to Major Intrinsic Protein Family, facilitate these across membranes. MTPs including aquaporins and carrier are transmembrane spanning The easy handling microorganisms enabled discovery a remarkable number specific different substances. It has been realized that transporters have very important roles in survival microorganisms, their pathogenesis, antimicrobial resistance. Astonishing features related solute specificity led acceleration research on properties development innovative products unique used or imitated. Studies microbial range from characterization novel transporter protein mining screening them large library particular functions, simulations modeling preparation biomimetic synthetic materials purposes such as biosensors filtration This review presents recent discoveries focuses especially formate nitrite aquaporins, advances biotechnological applications.

Language: Английский

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Calcium‐dependent antimicrobials: Nature‐inspired materials and designs

Exploration, Journal Year: 2024, Volume and Issue: 4(5)

Published: March 12, 2024

Abstract Bacterial infection remains a major complication answering for the failures of various implantable medical devices. Tremendous extraordinary advances have been published in design and synthesis antimicrobial materials addressing this issue; however, clinical translation has largely blocked due to challenge balancing efficacy safety these materials. Here, calcium's biochemical features, natural roles pathogens immune systems, advanced uses medications are illuminated, showing calcium is promising target developing devices with less tendency. The paper gives historical overview biomedical summarizes merits coordination, hydration, ionization, stereochemistry acting as structural former or trigger biological systems. It focuses on involvement pathogens’ integrity, motility, metabolism maintenance, outlining potential targets calcium. addresses systems that authors can learn from synthesis. Additionally, highlighted sketch future directions In conclusion, at nexus defense, works taking advantage developments translation.

Language: Английский

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cGAMP the travelling messenger

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 23, 2023

2’3’-cGAMP is a key molecule in the cGAS-STING pathway. This cyclic dinucleotide produced by cytosolic DNA sensor cGAS response to presence of aberrant dsDNA cytoplasm which associated with microbial invasion or cellular damage. acts as second messenger and activates STING, central hub sensing, induce type-I interferons pro-inflammatory cytokines necessary for responses against infection, cancer stress. Classically, detection pathogens danger pattern recognition receptors (PRR) was thought signal production interferon cell where sensing occurred. These then both an autocrine paracrine manner neighboring cells. Deviating from this dogma, recent studies have identified multiple mechanisms can travel cells it STING independent cGAS. observation great importance, pathway involved immune invaders while its dysregulation drives pathology wide range inflammatory diseases antagonists been elusive. In review, we describe fast-paced discoveries be transported. We further highlight they are important detail how change perspective applied vaccine design, immunotherapies treatment disease.

Language: Английский

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Atomic structure of the open SARS-CoV-2 E viroporin

Science Advances, Journal Year: 2023, Volume and Issue: 9(41)

Published: Oct. 13, 2023

The envelope (E) protein of the SARS-CoV-2 virus forms cation-conducting channels in endoplasmic reticulum Golgi intermediate compartment (ERGIC) infected cells. calcium channel activity E is associated with inflammatory responses COVID-19. Using solid-state NMR (ssNMR) spectroscopy, we have determined open-state structure E’s transmembrane domain (ETM) lipid bilayers. Compared to closed state, open ETM has an expansive water-filled amino-terminal chamber capped by key glutamate and threonine residues, a loose phenylalanine aromatic belt middle, constricted polar carboxyl-terminal pore filled arginine residue. This gives insights into how protons ions are selected they permeate across hydrophobic gate this viroporin.

Language: Английский

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The Envelope (E) Protein of SARS-CoV-2 as a Pharmacological Target

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 1000 - 1000

Published: April 19, 2023

The COVID-19 pandemic caused by the SARS-CoV-2 virus is still a global health concern. Several spike (S) protein-based vaccines have been developed that efficiently protect human population against severe forms of COVID-19. However, some variants concern (VOCs) emerged evade protective effect vaccine-induced antibodies. Therefore, efficient and specific antiviral treatments to control are indispensable. To date, two drugs approved for mild treatment; nevertheless, more drugs, preferably broad-spectrum ready-to-use therapeutic agents new pandemics, needed. Here, I discuss PDZ-dependent protein-protein interactions viral E protein with host proteins as attractive alternatives development antivirals coronavirus.

Language: Английский

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SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Pathogens, Journal Year: 2024, Volume and Issue: 13(1), P. 75 - 75

Published: Jan. 14, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability mutate, high mortality and morbidity, enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue emerge. Antiviral medications offer a viable alternative, success been inconsistent. Therefore, there remains an ongoing need identify innovative antiviral drugs for treating post-infection ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents promising target treatment multifaceted role viral pathogenesis, cytokine storms, disease severity, mortality. contributes significantly pathogenesis facilitating assembly release, essential processes the life cycle, also suppressing body’s responses, thus aiding replication. implicated triggering excessive inflammation, characterized NF-κB-mediated production, ultimately leading apoptotic cell death tissue damage lungs, kidneys, central nervous system. Additionally, triggers activation of NLRP3 inflammasome, inciting storm, which is major contributor severity subsequent As with spike protein, undergoes mutations, certain mutant correlate heightened COVID-19. These mutations may influence replication host cellular inflammatory responses. While establishing direct link between difficult, involvement promoting inflammation exacerbating likely higher rates severe cases. This review offers comprehensive detailed exploration ORF3a’s potential as drug target. we outline strategies discovering developing inhibitor counteract harmful effects, alleviate damage, reduce lingering

Language: Английский

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Viroporins Manipulate Cellular Powerhouses and Modulate Innate Immunity

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 345 - 345

Published: Feb. 23, 2024

Viruses have a wide repertoire of molecular strategies that focus on their replication or the facilitation different stages viral cycle. One these is mediated by activity viroporins, which are multifunctional proteins that, upon oligomerization, exhibit ion channel properties with mild selectivity. Viroporins facilitate multiple processes, such as regulation immune response and inflammasome activation through induction pore formation in various cell organelle membranes to escape ions alteration intracellular homeostasis. target diverse (such cellular membrane), endoplasmic reticulum, mitochondria. Cumulative data regarding importance mitochondria function metabolism, energy production, calcium homeostasis, apoptosis, mitophagy, been reported. The direct indirect interaction viroporins how this affects functioning mitochondrial cells innate immunity host against viruses remains unclear. A better understanding viroporin–mitochondria interactions will provide insights into role affecting signaling Thus, review, we mainly descriptions studies provided hijacked

Language: Английский

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Distinct motifs in the E protein are required for SARS-CoV-2 virus particle formation and lysosomal deacidification in host cells

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(10)

Published: Oct. 13, 2023

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused a global public health crisis. The E protein, structural protein found in this particle, is also known to be viroporin. As such, it forms oligomeric ion channels or pores host cell membrane. However, relationship between these two functions poorly understood. In study, we showed that roles of particle and viroporin formation are distinct. This study contributes development drugs inhibit SARS-CoV-2 formation. Additionally, designed highly sensitive high-throughput virus-like detection system using HiBiT tag, which useful tool studying release SARS-CoV-2.

Language: Английский

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