Emerging roles of SARS-CoV-2 Spike-ACE2 in immune evasion and pathogenesis

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(6), P. 424 - 434

Published: April 6, 2023

The COVID-19 pandemic, caused by SARS-CoV-2, has an estimated 5 billion infections and 20 million deaths respiratory failure. In addition to the disease, SARS-CoV-2 infection been associated with many extrapulmonary complications not easily explainable infection. A recent study showed that spike protein, which mediates cell entry binding angiotensin-converting enzyme 2 (ACE2) receptor, signals through ACE2 change host behavior. CD8+ T cells, spike-dependent ACE2-mediated signaling suppresses immunological synapse (IS) formation impairs their killing ability, leading immune escape of virus-infected cells. this opinion article, we discuss consequences on response propose it contributes manifestations COVID-19.

Language: Английский

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Bioinformatics approaches for unveiling virus-host interactions

Computational and Structural Biotechnology Journal, Journal Year: 2023, Volume and Issue: 21, P. 1774 - 1784

Published: Jan. 1, 2023

The coronavirus disease-2019 (COVID-19) pandemic has elucidated major limitations in the capacity of medical and research institutions to appropriately manage emerging infectious diseases. We can improve our understanding diseases by unveiling virus–host interactions through host range prediction protein–protein interaction prediction. Although many algorithms have been developed predict interactions, numerous issues remain be solved, entire network remains veiled. In this review, we comprehensively surveyed used interactions. also discuss current challenges, such as dataset biases toward highly pathogenic viruses, potential solutions. complete difficult; however, bioinformatics contribute progress on human health.

Language: Английский

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Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 13, 2023

The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to folded domain. Here, we used proteomic peptide phage display (ProP-PD) identify peptides from the intrinsically regions of human proteome that bind domains encoded by SARS-CoV-2 genome. Eleven proteins were found 281 proteins, and affinities 31 interactions involving eight determined (K

Language: Английский

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A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 22, 2024

Abstract The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers resistance. Therefore, there is pronounced interest in identifying new pharmacological targets viral life cycle. small molecule PAV-104, identified through a cell-free protein synthesis assembly screen, was recently shown target host machinery manner specific assembly. In this study, we investigate capacity PAV-104 inhibit replication human airway epithelial cells (AECs). We show that inhibits >99% infection diverse variants immortalized AECs, primary AECs cultured at air-liquid interface (ALI) represent lung microenvironment vivo. Our data demonstrate production without affecting entry, mRNA transcription, or synthesis. interacts nucleocapsid (N) interferes its oligomerization, blocking particle Transcriptomic analysis reveals reverses induction type-I interferon response maturation nucleoprotein signaling pathway known support coronavirus replication. findings suggest promising therapeutic candidate COVID-19 mechanism action distinct from existing clinical management approaches.

Language: Английский

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Metabolic and mitochondria alterations induced by SARS‐CoV‐2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(7)

Published: July 1, 2024

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c ORF10 induce a significant mitochondrial metabolic reprogramming in A549 lung epithelial cells. While induced largely overlapping transcriptomes, ORF3a distinct transcriptome, including downregulation numerous genes with critical roles function morphology. On other hand, all four ORFs altered dynamics function, but only marked alteration cristae structure. Genome-Scale Metabolic Models identified both flux features shared across specific for each protein. Notably, downregulated amino acid was observed ORF10, while an upregulated lipid distinctly ORF3a. These findings reveal dependencies vulnerabilities prompted may be exploited to identify new targets intervention.

Language: Английский

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Dual action anti‐inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti‐SARS‐CoV‐2 agents: A combined pharmacological and medicinal chemistry perspective

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(5), P. 2168 - 2186

Published: April 11, 2023

Abstract In the search for compounds that inhibit SARS‐CoV‐2 after onset of COVID‐19 pandemic, isoquinoline‐containing alkaloids have been identified as with high potential to fight disease. addition having strong antiviral activities, most these significant anti‐inflammatory effects which are often manifested through inhibition a promising host‐based anti‐COVID‐19 target, p38 MAPK signaling pathway. present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting anti‐SARS‐CoV‐2 isoquinoline‐based treatment patients. Considering critical parameters mechanism action, well toxicity/safety profile, we introduce emetine, cephaeline, papaverine high‐potential therapeutic agents use COVID‐19. Although preclinical studies confirm some reviewed this study SARS‐CoV‐2, their entry into drug regimens patients requires further clinical trial toxicity evaluation.

Language: Английский

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Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 14, 2023

The coronavirus disease 2019 (COVID-19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that rapidly evolving subvariants risk rendering vaccines antibodies ineffective due to their potential evade existing immunity, with enhanced transmission activity higher reinfection rates could lead new outbreaks across globe. goal viral management is disrupt life cycle as well relieve severe symptoms such lung damage, cytokine storm, organ failure. In fight against viruses, combination genome sequencing, elucidation structure proteins, identifying proteins are highly conserved multiple coronaviruses revealed many molecular targets. addition, time- cost-effective repurposing preexisting antiviral drugs or approved/clinical for these targets offers considerable clinical advantages COVID-19 patients. This review provides comprehensive overview various identified pathogenic pathways corresponding repurposed COVID-19. These findings provide insight into discovery novel therapeutic strategies be applied control emanating from SARS-CoV-2 variants.

Language: Английский

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HNSPPI: a hybrid computational model combing network and sequence information for predicting protein–protein interaction

Briefings in Bioinformatics, Journal Year: 2023, Volume and Issue: 24(5)

Published: June 28, 2023

Most life activities in organisms are regulated through protein complexes, which mainly controlled via Protein-Protein Interactions (PPIs). Discovering new interactions between proteins and revealing their biological functions of great significance for understanding the molecular mechanisms processes identifying potential targets drug discovery. Current experimental methods only capture stable interactions, lead to limited coverage. In addition, expensive cost time consuming also obvious shortcomings. recent years, various computational have been successfully developed predicting PPIs based on homology, primary sequences or gene ontology information. Computational efficiency data complexity still main bottlenecks algorithm generalization. this study, we proposed a novel framework, HNSPPI, predict PPIs. As hybrid supervised learning model, HNSPPI comprehensively characterizes intrinsic relationship two by integrating amino acid sequence information connection properties PPI network. The results show that works very well six benchmark datasets. Moreover, comparison analysis proved our model significantly outperforms other five existing algorithms. Finally, used explore SARS-CoV-2-Human interaction system found several regulations. summary, is promising from known data.

Language: Английский

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4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: 24(2), P. 499 - 514

Published: Jan. 13, 2025

Since late 2021, Omicron variants have dominated the epidemiological scenario as most successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineages, driving new and breakthrough infections globally over past two years. In this study, we investigated for first time host salivary response of COVID-19 patients infected with (BA.1, BA.2, BA.4/5) by using an untargeted four-dimensional data-independent acquisition (4D-DIA)-based proteomics approach. We identified 137 proteins whose abundance levels differed between positive negative groups. Salivary signatures were mainly enriched in ribosomal proteins, linked to mRNAviral translation, protein synthesis processing, immune innate, antiapoptotic signaling. The higher 14-3-3 (YWHAG, YWHAQ, YWHAE, SFN) saliva, reported here, may be associated increased infectivity improved viral replicative fitness. also seven (ACTN1, H2AC2, GSN, NDKA, CD109, GGH, PCYOX) that yielded comprehension into infection performed outstandingly screening a hospital setting. This panel presented enhanced anti-COVID-19 anti-inflammatory signature, providing insights disease severity, supported comparisons other proteome data sets. signature provided valuable host's SARS-CoV-2 infection, shedding light on pathophysiology COVID-19, particularly cases mild disease. It underscores potential clinical applications saliva settings. Data are available via ProteomeXchange identifier PXD054133.

Language: Английский

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Potential Involvement of Protein Phosphatase PPP2CA on Protein Synthesis and Cell Cycle During SARS-CoV-2 Infection: A Meta-Analysis Investigation

Kinases and Phosphatases, Journal Year: 2025, Volume and Issue: 3(1), P. 4 - 4

Published: Feb. 18, 2025

Coronavirus disease 2019 is a multi-systemic syndrome that caused pandemic. Proteomic studies have shown changes in protein expression and interaction involved signaling pathways related to SARS-CoV-2 infections. Protein phosphatases play crucial role regulating cell signaling. In this study, we assessed the potential involvement of their associated during infection by conducting meta-analysis proteome databases from COVID-19 patients. We identified both direct indirect interactions between human viral proteins, as well levels phosphorylation status intermediate proteins. Our analyses revealed PPP2CA PTEN are key cycle apoptosis regulation infection. also highlighted division throughout its with CDC20 (cell 20 homolog). This evidence strongly suggests proteins critical roles represent targets for treatment.

Language: Английский

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