Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets

Farahani, Masoumeh; Niknam, Zahra; Amirabad, Leila Mohammadi; Amiri-Dashatan, Nasrin; Koushki, Mehdi; Nemati, Mohadeseh; Pouya, Fahima Danesh; Rezaei‐Tavirani, Mostafa; Rasmi, Yousef; Tayebi, Lobat

doi:10.1016/j.biopha.2021.112420

Cited by 92 publications

(99 citation statements)

References 260 publications

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“…Our study revealed that the Jak-STAT signaling pathway 19 , Cytokine-Cytokine receptor interactions 20 , MAPK signaling pathway 21 , Lung Fibrosis [22][23][24] , Chemokine signaling pathway 22 , Toll-like receptor signaling are the major pathways that were represented by identi ed DEGs and GO analysis. These pathways are well known and reported previously to play a crucial role in SARS-CoV-2 associated pathophysiology (Fig.…”

Section: Identi Cation Of Degsmentioning

confidence: 83%

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

Sharma¹,

Sharma²,

Chandil³

2022

Preprint

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Background It has been almost 2 years since the first SARS-CoV-2 virus was first reported in the city of Wuhan. So far, 8 drugs are approved against Covid-19 by FDA, however, an active drug against multi-mutational Covid-19 is still missing. In this present study, we aim to identify the most crucial and highly correlated protein targets from the publicly available transcriptomics datasets. Methods Transcriptomics datasets were retrieved from Geo Omnibus (GEO). We use relevant datasets to identify the most significant and differentially expressed genes and integrated them into a Research graph called CovInt (a network of Covid-19) that includes all biological molecules associated in the network with their directionalities collected from publicly available and patient-derived multi-omics datasets from millions of unstructured and structured datasets such as publications, patents, grants, preclinical and clinical reports. CovInt utilizes powerful traversal, clustering and centrality algorithms to identify key connections in the pathophysiology of the disease and its treatments. Results Leveraging 3M + connections, important interactions among key 42 drugs, 962 biological processes and molecular functions, 926 pathways, 897 phenotypes, 7103 proteins, 61 tissues were identified. This narrowed interactome was explored further using PageRank, lovain detection & strongly connected components (SSC) algorithms. In our analysis 63, strongly connected communities were identified which gives us an understanding of hidden underlying mechanisms. We further explored this network to identify and triangulate the key proteins, metabolic pathways and associated risk factors that can regulate moderate to severe Covid-19 infections. Conclusions Our study suggests that CREB3L1, SOX2, UBR4, FLNC, ITPA, DLG3, ING4, TECR, NADH, SMAD, HUWE1, DDX17, CREBBP, RELA, HPSE, TRIM33, TNFSF13B are the key regulator proteins and involved in ER-stress, cytokine signaling, T-Cell activation, Activation of NLRP3 Inflammation by SARS-CoV-2, JAK-STAT, IL-4, IL-13 pathways, MAPK signaling pathways, Activation of NMDA receptor & postsynaptic events and TGF-β signaling pathways.

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Section: Identi Cation Of Degsmentioning

confidence: 83%

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

Sharma¹,

Sharma²,

Chandil³

2022

Preprint

View full text Add to dashboard Cite

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“…While the commercial method of producing viral vectors for gene therapy was created decades ago, the complexity of viruses needs optimization for particular products to satisfy quality and cost-effectiveness criteria. A bottleneck of virus vector production is the scaling-up of virus production capacity [10,27]. To achieve scaling up, a suspension expression system cultured in a bioreactor may be used to replace the adherent cells grown in cell stacks [10].…”

Section: Recombinant Viral-vectored Vaccinesmentioning

confidence: 99%

Current advances and challenges in COVID-19 vaccine development: from conventional vaccines to next-generation vaccine platforms

et al. 2022

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The world is grappling with an unprecedented public health crisis COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. Due to the high transmission/mortality rates and socioeconomic impacts of the COVID-19, its control is crucial. In the absence of specific treatment, vaccines represent the most efficient way to control and stop the pandemic. Many companies around the world are currently making efforts to develop the vaccine to combat COVID-19. This review outlines key strategies for generating SARS-CoV-2 vaccine candidates, along with the mechanism of action, advantages, and potential limitations of each vaccine. The use of nanomaterials and nanotechnology for COVID-19 vaccines development will also be discussed. Keywords SARS-CoV-2 • COVID -19 vaccine platform • Vaccine candidate • Vaccine efficacy • Nanoparticles-based vaccine Abbreviations ACE2Angiotensin converting enzyme 2 APC Antigen-presenting cell ChAdOx1Chimpanzee adenoviral vector 1 COVID-19 Coronavirus disease-19 CQD Carbon quantum dots LNP Lipid nanoparticles ID Intradermal IM Intramuscular MERS Middle east respiratory syndrome RBD Receptor binding domain SARS-CoV-2 Severe acute respiratory syndrome coronavirus-2 SC Subcutaneous siRNA Small interfering RNA TLR Toll-like receptor VLP Virus-like particle * Mostafa Rezaei-Tavirani

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“…SARS-CoV-2 activates both innate and acquired immune response. Infected endothelial cells, mononuclear macrophages, neutrophils and maturated dendritic cells (innate immunity) produce pro-inflammatory mediators, such as interferon (IFN), cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and chemokines which recruit other components of the immune system [3]. The subsequent acquired immune responses including T lymphocytes (CD4 + and CD8 + T cells) and B lymphocytes play an important role in the defense.…”

Section: Corona Virus Disease 2019 (Covid -19mentioning

confidence: 99%

“…Excessive neutrophil extracellular traps production, by neutrophils, can enhance tissue damage and may contribute to cytokine storm, while activated B cells may contribute by production of IL-6. In patients with severe COVID-19 cytokine storm causes acute respiratory distress syndrome or multiple-organ dysfunction [3].…”

Section: Corona Virus Disease 2019 (Covid -19mentioning

confidence: 99%

Efficacy of intravenous immunoglobulin in the treatment of a COVID-19 patient

et al. 2022

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Introduction. Diabetes mellitus patients represent vulnerable group of people who are prone to getting infected with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The virus has a high binding affinity to angiotensin-converting enzyme 2 receptor which allows efficient host cell entering, prolonged virus retention and possibility of insulin resistance and ketoacidosis development. Case outline. We describe a case of a 20-year-old patient with a past medical history of type-1 diabetes mellitus who presented with bilateral COVID-19 pneumonia. Initially treatment with polyvitamin therapy, corticosteroids, tocilizumab and convalescent plasma did not improve the patient condition, but might have led to the worsening of underlying disease, high blood glucose level and ketoacidosis. Patient developed a rapid progression of the disease and severe pneumonia that required intubation and mechanical ventilation. Intravenous immunoglobulin (IVIg) has been administrated in order to suppress a hyperactive immune response through its immunomodulatory effect. Forty-eight hours later respiratory gas exchange had been improved, almost complete regression of changes in the lungs have been seen, normalization of metabolic and gas exchange parameters have been detected. After 14 days in the hospital the patient was discharged home in good general condition. Conclusion. COVID-19 complicated by diabetes mellitus leads to a poor outcome of the disease, but antiviral and anti-inflammatory activity of IVIg suggests that they may be useful therapeutic agent and in the case of COVID-19. In the presented case, the application of IVIg very fast led to an improvement in the patient?s condition.

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Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets

Cited by 92 publications

References 260 publications

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

Current advances and challenges in COVID-19 vaccine development: from conventional vaccines to next-generation vaccine platforms

Efficacy of intravenous immunoglobulin in the treatment of a COVID-19 patient

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